Guerrero debuted in World Championship Wrestling (WCW) in 1989 as a jobber, most notably wrestling Terry Funk. In 1991, he would return for WrestleWar, wrestling a dark match, teaming with Ultraman to defeat Huichol and Rudy Boy Gonzalez.
Guerrero won the ECW World Television Championship from 2 Cold Scorpio in his debut match for Extreme Championship Wrestling, and went on to have a series of acclaimed matches with Dean Malenko before they both signed with World Championship Wrestling later that year. Guerrero lost the ECW Television Championship to Malenko on July 21 of that year, but Guerrero regained the title on July 28. Guerrero lost the ECW Television Championship back to 2 Cold Scorpio on August 25. The next day, they had their last match which ended in a draw in a two out of three falls match at the ECW Arena.
Guerrero returned to WCW in late 1995 along with Dean Malenko and Chris Benoit with whom he had worked with in ECW. During his first few pay-per-view events, he competed in dark matches against Alex Wright. His first televised pay-per-view appearance was at World War 3 where he competed in the 3-ring, 60-man World War 3 battle royal for the vacant WCW World Heavyweight Championship. Guerrero was one of the final nine men in the battle royal until he was tossed out of the ring by Four Horsemen members. At Starrcade: World Cup of Wrestling in December 1995, Guerrero represented WCW in a World Cup tournament, which saw him losing to Shinjiro Otani in the match, but Team WCW would go on to win the series at 4–3.
In 1996, Guerrero received several shots at the United States Heavyweight Championship against Konnan at Uncensored and Ric Flair at Hog Wild. He feuded with Ric Flair and the Four Horsemen during 1996 after Guerrero's partner Arn Anderson turned on him during a tag team match against Ric Flair and Randy Savage. In late 1996, he feuded with Diamond Dallas Page after defeating him in a match at Clash of the Champions XXXIII. He started feuding with DDP to steal his nickname of "Lord of the Ring", but lost. Guerrero participated in a tournament for the vacant WCW United States Heavyweight Championship and defeated DDP in the final round at Starrcade to win the United States title in December 1996.
In 1997, Guerrero defended the United States Heavyweight Championship against Scott Norton at Clash of the Champions XXXIV, Syxx in a ladder match at Souled Out, and Chris Jericho at SuperBrawl VII. His reign came to an end at Uncensored when Dean Malenko defeated him for the title.
After losing the United States Heavyweight Championship, Guerrero feuded with Jericho focusing on Jericho's Cruiserweight Championship. He challenged Jericho for the title at Clash of the Champions XXXV but lost. Guerrero demanded a rematch for the title. In the opening match of Fall Brawl, Guerrero defeated Jericho to win the WCW World Cruiserweight Championship. He dropped the Cruiserweight title to Rey Mysterio Jr. at Halloween Havoc in a title vs. mask match where Mysterio's mask was also on the line. On the November 10 episode of Monday Nitro, he regained the Cruiserweight title from Mysterio, and made a successful title defense against Mysterio at World War 3. After retaining the title against Dean Malenko in the opening bout of Starrcade in December 1997, Guerrero dropped the title to Último Dragón the following day on the December 29 episode of Nitro.
On the March 9, 1998 episode of Nitro, Guerrero's nephew Chavo Guerrero lost to Booker T in a match. After the match, Guerrero suplexed Chavo to teach him a lesson. On the March 12 episode of Thunder, he defeated his nephew Chavo in a match and forced him to become his "slave". At Uncensored, Chavo was forced to support Guerrero when he faced Booker T for Booker's WCW World Television Championship. Guerrero lost the match after receiving a missile dropkick. Guerrero and Chavo feuded with Último Dragón. Chavo lost to Dragón at Spring Stampede. At Slamboree, Guerrero defeated Dragón despite interference from Chavo. After the match, Chavo kissed Eddie and began to display insane behavior. At The Great American Bash, Chavo got an upset victory over Guerrero. They faced each other in a hair vs. hair match at Bash at the Beach which Guerrero won. Continuing to show his crazy behavior, Chavo would shave his own head while Guerrero looked on in disbelief. Guerrero saved Chavo from beatings by Stevie Ray, seeming that he would align with Chavo but he wanted his release.
After a brief departure from WCW due to a heated confrontation with Eric Bischoff, Guerrero soon returned and formed the Latino World Order (LWO), which was a take-off of Bischoff's New World Order. The LWO was formed in October when Guerrero returned to WCW, with Héctor Garza and Damien. The group eventually grew to encompass almost all the Mexican wrestlers working for WCW at the time. They mainly feuded with Rey Mysterio Jr. and Billy Kidman because they wanted Mysterio to join the group. He faced Kidman in a match for the WCW Cruiserweight Championship but Mysterio interfered and helped Kidman win the match and keep the title. However, Guerrero was involved in a car accident on New Year's Day 1999 that cut short the LWO storyline.
After his return on the May 31, 1999 episode of Monday Nitro, Guerrero became a founding member of The Filthy Animals alongside Rey Mysterio Jr. and Konnan. They feuded with the Dead Pool (Insane Clown Posse and Vampiro). They received two straight victories over the Dead Pool at Road Wild and Fall Brawl. They next feuded with The Revolution (Shane Douglas, Chris Benoit, Dean Malenko, and Perry Saturn). Guerrero was victorious over Saturn by disqualification in a singles match at Halloween Havoc. At Mayhem, the Animals lost to Revolution in a mixed tag team elimination match. Guerrero asked for and received a release from his contract on January 19, 2000. He signed with the World Wrestling Federation (WWF) in 2000 along with fellow WCW stars Benoit, Malenko, and Saturn.
Guerrero, Chris Benoit, Dean Malenko and Perry Saturn debuted in the WWF on the January 31, 2000 episode of Raw Is War as The Radicalz, interfering in a match involving The New Age Outlaws, establishing themselves as faces. During his first match with the WWF, a tag team match with Perry Saturn against The New Age Outlaws, Guerrero performed a frog splash off the top rope and dislocated his elbow when he landed the move; as a result, he was sidelined for several weeks.
In March, Guerrero, who was wrestling as a heel, began pursuing the affections of Chyna, who he referred to as his "Mamacita". At the time, Chyna was allies with Chris Jericho and initially rejected his advances. The night after WrestleMania 2000, on the April 3, 2000 episode of Raw Is War, Guerrero faced off against Jericho for the European Championship. During the match, Chyna turned on Jericho and helped Guerrero win, and later explained her actions by declaring that she could not resist his "Latino Heat". After Chyna abandoned Lita to be attacked by The Dudley Boyz, he and Chyna began a feud with Essa Rios and Lita, ending in a European title defense at Backlash. Guerrero defeated Rios after arriving at ringside in a 1957 Chevrolet, wrestling in a tuxedo pants and a bow tie. Guerrero turned face and successfully retained the title against former Radicalz friends Saturn and Malenko in a triple threat match at Judgment Day, before losing the title to Saturn at Fully Loaded. The two slowly began to become popular with the fans, but over the next few months friction began to build between Guerrero and Chyna.
Chyna was upset when Guerrero pinned her to advance in the King of the Ring tournament. Then at SummerSlam that August, Guerrero and Chyna wrestled a mixed tag team match against Trish Stratus and Val Venis, who at the time was the reigning Intercontinental Champion. The Intercontinental Championship was on the line in the match, and whoever scored the pin would win the title. Guerrero's team won the match, but Chyna scored the pin on Trish and became a two-time Intercontinental Champion. Although Guerrero said he did not mind that his partner was the champion, on the September 4 episode of Raw Is War he went to WWF Commissioner Mick Foley and asked to be inserted into Chyna's title defense against Kurt Angle claiming that he did not want Angle to hurt his "mamacita". During the course of the match, Angle knocked down Chyna with the title belt and Guerrero laid on top of her to try to revive her. However, this resulted in Guerrero "accidentally" pinning Chyna as her shoulders were still on the mat, and thus Guerrero won the match and his first Intercontinental Championship. Chyna became visibly uncomfortable as Guerrero began to cheat in order to retain his title, while Guerrero was upset that Chyna was posing for Playboy magazine, even trying to invade the Playboy Mansion to stop the photo shoot. Just when it appeared that Chyna would leave Guerrero, he proposed to her and she accepted. At Unforgiven, Chyna helped Guerrero in retaining his title against Rikishi. The engagement was called off when Guerrero was caught showering with two of The Godfather's hos (one was Victoria) claiming that "two Mamacitas are better than one".
Guerrero turned heel again as a result of the incident. Then, The Radicalz reunited and feuded with the reformed D-Generation X (Chyna, Billy Gunn, Road Dogg, and K-Kwik). They defeated D-Generation X at Survivor Series in an elimination tag team match and assisted Triple H in his match with Stone Cold Steve Austin. Guerrero was later defeated by Gunn for the Intercontinental Championship on the Thanksgiving episode of SmackDown!. At Rebellion, Guerrero and Malenko lost to Gunn and Chyna. Benoit left the group to focus on a singles career while the rest of The Radicalz feuded with Lita and The Hardy Boyz (Matt and Jeff). At Armageddon, The Radicalz defeated The Hardy Boyz and Lita in an elimination tag team match.
In early 2001, Guerrero feuded with Chris Jericho, Benoit, and X-Pac over Jericho's Intercontinental Championship. At No Way Out, the four men faced each other in a fatal four-way match, which Jericho won. Guerrero focused on the European Championship, feuding with the champion Test, and defeating him at WrestleMania X-Seven to win his second European Championship with help from Saturn and Malenko. In April, The Radicalz feuded with Test and his partners. Guerrero eventually left the Radicalz, siding with The Hardy Boyz and Lita. At this point, Guerrero developed an addiction to pain medication stemming from his 1999 car accident and in May 2001 was sent to rehab. To explain his absence, a storyline was created where Guerrero was "injured" by Albert in a match. On November 12, 2001, Guerrero was released by the WWF.
Guerrero returned to the WWF on the April 1, 2002 episode of Raw, attacking Rob Van Dam. He feuded with Van Dam, defeating him for his second Intercontinental Championship at Backlash. After retaining the title against Van Dam at Insurrextion and Judgment Day, he finally lost the title to Van Dam on the May 27 episode of Raw in a ladder match. Guerrero then feuded with Stone Cold Steve Austin, but Austin left the WWE before a match could take place. Chris Benoit returned to WWE the night Guerrero lost the title and reunited with him. Guerrero and Benoit feuded with Ric Flair for a while and Guerrero lost a match to Flair at King of the Ring.
On August 1, 2002, Guerrero and Benoit moved to WWE's SmackDown! brand. Guerrero feuded with Edge, to whom he lost at SummerSlam. Guerrero continued his feud with Edge, whom he defeated at Unforgiven; they then had a no disqualification match four days after Unforgiven on SmackDown! which Edge won thus ending the rivalry.
With Benoit focusing on Kurt Angle, Guerrero aligned himself with his nephew Chavo, forming the tag team Los Guerreros. In contrast to a previous WCW storyline with his nephew, Chavo fully agreed with his uncle as their slogan stated: "We lie, we cheat, and we steal, but at least we're honest about it". In order to push the new tag team, vignettes were produced, which included things such as the two finagling their way into a rich lady's house and throwing a pool party. These segments marked the beginning of the rise of popularity for the team, especially Eddie, who continued to use the mannerisms.
The duo entered the eight-team tournament for the new WWE Tag Team Championship, sneaking past Rikishi and Mark Henry in the opening round, before starting a feud with the newly formed tag team of Kurt Angle and Chris Benoit. In one of the team's definitive moments, Chavo told Benoit that his former friend Guerrero was assaulted by his tag team partner Angle. Benoit ran to make the save, only to have himself locked inside a room. Guerrero then appeared in the room and assaulted Benoit with a steel chair. Benoit and Angle managed to overcome their differences and eventually defeated Los Guerreros in the tournament semi-finals. Later on, Benoit and Angle won the titles. Benoit and Angle then fought for a trophy for being the first WWE Tag Team Champions. Much to Benoit's surprise, Los Guerreros helped him win the match.
At Survivor Series, Los Guerreros faced the new champions Edge and Rey Mysterio and the team of Angle and Benoit for the titles. Guerrero made Mysterio submit to the Lasso from El Paso to win their first WWE Tag Team Championship. They turned face due to their popularity. They lost the titles to Team Angle (Charlie Haas and Shelton Benjamin) on the February 6, 2003 episode of SmackDown!. Los Guerreros and Team Angle began feuding with each other. Los Guerreros participated at WrestleMania XIX as contenders for the Tag Team Titles, along with the team of Benoit and Rhyno. Both teams lost to Haas and Benjamin in a triple threat match. At Backlash, Los Guerreros lost to Team Angle in a rematch.
Five days prior to Judgment Day, Chavo tore his biceps, forcing Guerrero to look for another partner. He chose Tajiri, and they won the WWE Tag Team Championship, Guerrero's second and Tajiri's first at Judgment Day by defeating Team Angle in a ladder match. The following week, Guerrero and Tajiri managed to retain their titles by cheating. They also defeated Roddy Piper and his protégé Sean O'Haire in Madison Square Garden. After Guerrero and Tajiri lost the titles to The World's Greatest Tag Team (previously Team Angle) on the July 3 episode of SmackDown!, Guerrero turned on Tajiri, slamming his partner through the windshield of his low-rider truck, turning heel once again. On the next SmackDown! Guerrero said he did it because during the match Tajiri had accidentally hit his low-rider. Despite being portrayed as the heel, when Guerrero asked the audience if they blamed him for doing it, the audience responded by yelling "No!".
In July 2003, Guerrero competed in a tournament for the WWE United States Championship. He managed to advance to the final round, defeating Último Dragón and Billy Gunn in the process, where he would meet Chris Benoit. At Vengeance, Guerrero turned to his cheating tactics, hitting Benoit with the belt at one point in the match. Guerrero tried to get Benoit in trouble by placing the title belt on top of the unconscious Benoit. It did not work, however, since he knocked out the referee earlier with a championship belt shot to the kidneys. The match ended with interference and a Gore from Rhyno, Benoit's own partner, who was furious at the team's failure.
At SummerSlam, Guerrero retained his title by defeating Rhyno, Benoit, and Tajiri in a fatal four-way match. He turned face again by engaging in a rivalry with John Cena. On the September 11 episode of SmackDown!, Guerrero challenged Cena to a "Latino Heat" Parking Lot Brawl match for the United States Championship, which Guerrero won with help from his returning nephew, Chavo. The next week on SmackDown!, Los Guerreros defeated The World's Greatest Tag Team to win the WWE Tag Team Championship, making Guerrero a double champion (beginning Guerrero's third tag title reign).
Guerrero then engaged in a feud with Big Show, which involved Guerrero giving Big Show some laxative laced burritos and then later spraying Show from a sewage truck. The feud ended when Guerrero lost the United States Championship to Big Show at No Mercy. Four days later, Los Guerreros lost the WWE Tag Team Championship to the Basham Brothers (Danny and Doug). They began feuding with the Basham Brothers, but failed to regain the championship at Survivor Series. As Los Guerreros attempted to regain the tag team titles, things began to go downhill between Chavo and Eddie, as animosity began to build. Chavo then attacked and turned on Guerrero after he suffered a beating from The Bashams. Guerrero feuded with Chavo and defeated him at the Royal Rumble to settle their feud. After the match Eddie attacked Chavo causing him to bleed.
When Chris Benoit jumped to the Raw brand after winning the Royal Rumble match, using his title shot to go for Triple H's World Heavyweight Championship, Guerrero won a 15-man Royal Rumble match on the January 29, 2004 episode of SmackDown! to earn a shot at the WWE Championship. After becoming the number one contender, Guerrero elevated himself to main event status and began feuding with the WWE Champion Brock Lesnar. At No Way Out, Guerrero defeated Lesnar in a shocking upset victory in the main event to win the WWE Championship. The victory made him a Triple Crown and Grand Slam Champion in the process. His next feud was with Kurt Angle, whom he defeated at WrestleMania XX to retain his title in his first big defense. At the end of this event, Guerrero celebrated in the ring with longtime friend Chris Benoit, who had just won the World Heavyweight Championship.
In March, he started a feud with fellow Texan John "Bradshaw" Layfield (JBL) after JBL interrupted Guerrero's title match with Booker T. The rivalry would soon turn personal when at a non-televised live event, JBL caused Guerrero's mother to suffer a (kayfabe) heart attack while in attendance at ringside. At Judgment Day, Guerrero defended his WWE title against JBL, retaining the title after getting himself disqualified, hitting JBL with the championship title. The match witnessed Guerrero bleed heavily mid-way in the match as a result of Guerrero performing a bladejob after a stiff headshot ringside with a chair from JBL. It was later explained that he cut too deep, thus hitting an artery. After the match concluded, Guerrero went into shock and passed out backstage and was taken to a nearby medical facility.
A few days after Judgment Day on the following episode of SmackDown!, Guerrero, Rey Mysterio, and Rob Van Dam faced JBL and The Dudley Boyz in a tag-team match. During the match, Guerrero (kayfabe) collapsed in the ring. JBL, with confusion, played to the crowd as if he had no idea what was happening. Worried in that situation, JBL pinned Guerrero forcing the referee to count to three. At The Great American Bash, Guerrero defended the title against JBL in a Texas bullrope match. JBL won after Angle (who was General Manager of SmackDown! at the time) reversed the decision after Guerrero appeared to have retained the title. On the July 8 episode of SmackDown!, Guerrero pulled a switcharoo with Shannon Moore, who was wrestling as "El Gran Luchadore" and wore the costume. On the July 15 episode of SmackDown!, Guerrero faced JBL in a steel cage match for the WWE title where El Gran Luchadore appeared again and cost Guerrero the match; he later revealed himself as Kurt Angle. Guerrero continued his feud with Angle. At SummerSlam, Guerrero lost to Angle after submitting to his ankle lock. Guerrero then allied himself with Big Show. Each week Angle and his new allies Luther Reigns and Mark Jindrak began targeting Guerrero and Big Show. Guerrero defeated Reigns in a singles match at No Mercy. General Manager Theodore Long booked a Survivor Series Elimination match between a team led by Guerrero and a team led by Angle. Guerrero's team consisted of himself, Big Show, John Cena (replacing the originally chosen Rey Mysterio), and Rob Van Dam. At Survivor Series, Guerrero's team defeated Angle's team. Guerrero, along with Booker T and The Undertaker, then challenged JBL for a WWE Championship rematch. Along the way, Guerrero found a partner in Booker T. At Armageddon, Guerrero and Booker's initial teamwork broke away, and the match ended with JBL pinning Booker following the Clothesline From Hell. Afterwards, Guerrero and Booker briefly and unsuccessfully attempted to win the WWE Tag Team Championship.
At the Royal Rumble, Guerrero entered at No. 1 and lasted 28:11 before being eliminated by Edge. In a skit before the Rumble, he drew his number the same time Ric Flair drew his. In an attempt to get a better draw, Guerrero switched his number with Flair's (and stole Flair's wallet in the process). Theodore Long made him return both items before the match. Flair would enter at No. 30. At No Way Out, Guerrero teamed up with longtime friend and sometimes rival, Rey Mysterio and defeated the Basham Brothers to win his final title, the WWE Tag Team Championship for a fourth time, with it being Mysterio's third reign. Many expected the new champions to defend their title at WrestleMania 21, but after encouragement from Chavo, Guerrero challenged Mysterio to a one-on-one match instead so they could "bring the house down". The two wrestled a match at WrestleMania with Mysterio getting the win. Although visibly frustrated, Guerrero congratulated his partner. After several mishaps in the weeks following WrestleMania, the growing tension between Guerrero and Mysterio finally erupted when they lost the WWE Tag Team Championship to the new team MNM (Johnny Nitro and Joey Mercury) on the April 21 episode of SmackDown!. Although the next week they received a rematch to regain the titles, Guerrero abandoned Mysterio, whom he had considered "his family" earlier in the show, costing them the match.
At the end of the May 5 episode of SmackDown!, he saved Mysterio from an attack by Chavo and MNM, before attacking Mysterio, leaving him bruised and bloody after suplexing him onto a set of steel steps thus turning heel in the process. Guerrero then adopted a new, brooding gimmick. During this time, he also stopped driving his low-riders down the ring and walked to the ring slowly with a frown on his face, gained a new theme which was a darker remix of "Lie, Cheat, And Steal" and started using his other finishing move, the Lasso from El Paso, more often. At Judgment Day, Guerrero lost to Mysterio by disqualification after hitting Mysterio with a chair.
On the June 30 episode of SmackDown!, Guerrero threatened to reveal a secret about Mysterio and his son Dominick. The storyline grew to involve the families of both men, with both sides pleading for Guerrero not to reveal the secret. Mysterio defeated Guerrero again at The Great American Bash, a match with a stipulation that if Guerrero lost, he would not tell the secret. Yet Guerrero revealed the secret anyway on the following episode of SmackDown! – telling Dominick and the audience that Guerrero was his real father. In the following weeks, Guerrero revealed the details of the secret in a series of what he called "Eddie's Bedtime Stories". During that time he now had a dark comical gimmick. He claimed that he had a child out of wedlock (Dominick) while his marriage was going through hard times. He claimed he then allowed Mysterio and his wife, who were "having trouble conceiving", to adopt the child as their own. At SummerSlam, Guerrero lost a ladder match over Dominick's custody to Mysterio. On the September 9 episode of SmackDown!, their feud ended when Guerrero defeated Mysterio in a steel cage match.
Following his feud with Mysterio, Guerrero was named number one contender to the World Heavyweight Championship and given a title match with Batista. Despite this, Guerrero quickly proclaimed himself to be Batista's friend. Batista was well aware of Guerrero's sneaky reputation, and despite eventually accepting his friendship (initially to keep an eye on him), Batista would continually play mind games with Guerrero to expose his true intentions. A series of matches with MNM only supported Batista's suspicions that Guerrero was up to no good, as Guerrero appeared to have reverted to his cheating ways. In response to Batista's suspicions, Guerrero helped Batista win a match against his tag team partners, JBL and Christian. Batista defeated Guerrero at No Mercy to retain the World Heavyweight Championship in what would be Guerrero's last pay-per-view match. During the match, Guerrero struggled with a decision about whether or not to use a steel chair to secure the victory, eventually opting not to use it and losing as a result. Though the two demonstrated mutual respect after the match, Guerrero seemed displeased by the loss. Guerrero told Batista that he realized how low he had sunk since losing the WWE Championship in 2004, having attacked his best friend Rey Mysterio. Guerrero told Batista that shaking his hand at No Mercy had returned his respect to him. After the match, Batista called Guerrero back out and sang "Happy Birthday" and, along with the crowd, celebrated Guerrero's 38th birthday. He would make his entrance the following SmackDown! using his signature low rider and old entrance theme with Batista, turning face again. He wrestled his last match on the November 11 SmackDown!, defeating Mr. Kennedy by disqualification using his signature lie, cheat, and steal tactics, which allowed him to advance to the SmackDown! Survivor Series team. On the date of his death, a triple threat match between himself, Batista, and Randy Orton was supposed to take place to air on the following episode of SmackDown! for the World Heavyweight Championship. Orton was given Guerrero's spot in the traditional Survivor Series elimination match between the Raw and SmackDown! brands, which SmackDown! would win, with Orton being the sole survivor.
On November 13, 2005, Guerrero was found unconscious in his hotel room at the Marriott Hotel City Center in Minneapolis, Minnesota, by his nephew, Chavo, who attempted CPR. Guerrero was pronounced dead when paramedics arrived at the scene.
The episodes of Raw on November 14 and SmackDown! on November 18 (both filmed November 13) each aired as tributes to Guerrero. All storylines were put on hold, and no WWE employees were forced to perform, although several matches took place, including one featuring Chavo, who finished the match with his uncle's finishing maneuver the frog splash. Raw started off with all the wrestlers and several personnel on stage, as Vince McMahon addressed the live crowd before finishing with a ten-bell salute.
The following year, on the night before WrestleMania 22, Guerrero was posthumously inducted into the WWE Hall of Fame.