At the age of 24, Henry made his first appearance on World Wrestling Federation (WWF) programming on the March 11, 1996 episode of Monday Night Raw, where he press slammed Jerry Lawler, who was ridiculing Henry while interviewing him in the ring. His first feud in the WWF was with Lawler. At the pay-per-view event, SummerSlam in August 1996, Henry came to the aid of Jake Roberts who was suffering indignity at the hands of Lawler. His debut wrestling match was at In Your House: Mind Games on September 22, 1996, where he defeated Lawler. The feud continued on the live circuit during subsequent weeks. On the November 4 episode of Raw, Henry served as a cornerman for Barry Windham in a match against Goldust. He was set to team with Windham, Marc Mero and Rocky Maivia to take on the team of Lawler, Goldust, Hunter Hearst Helmsley and Crush at Survivor Series, but was replaced by Jake Roberts when he was forced to withdraw from the event due to injury. On the November 17 episode of Superstars, Henry defeated Hunter Hearst Helmsley, Crush and Goldust in a tug of war contest. Henry's career was then stalled as, over the next year, he took time off to heal injuries and engage in further training. In November 1997, he returned to the ring, making his televised return the following month. By the end of the year, he was a regular fixture on WWF programming, defeating Steve Lombardi on the December 15 episode of Raw, and beating The Sultan on the December 27 episode of Shotgun.
Henry joined the faction with Faarooq, The Rock, Kama Mustafa, and D'Lo Brown on January 12, 1998. After The Rock usurped Faarooq's position as leader, Henry switched loyalties to The Rock. He also competed at WrestleMania XIV in a tag team battle royal with Brown as his partner, but they did not win. After short feuds against Ken Shamrock and Vader, Henry participated in his faction's enmity against D-Generation X, which included a romantic storyline with DX member Chyna. When The Nation disbanded, he engaged in a short feud with The Rock, defeating him at Judgment Day: In Your House with help from Brown, and then forming a permanent team with Brown, gaining Ivory as a manager.
During the next year, Henry gave himself the nickname "Sexual Chocolate", adopting a ladies' man character. He first resumed his storyline with former enemy Chyna, but it ended with her betraying him in a controversial angle including a transvestite. During a match at the August 1999 SummerSlam pay-per-view between Brown and Jeff Jarrett for the WWF Intercontinental and WWF European Championships (both held at the time by Brown), Henry turned on Brown and helped Jarrett win the match and the titles. The next night, Henry was awarded the European title by Jarrett in return for his help. Henry lost the title one month later to Brown at the Unforgiven pay-per-view.
The night after he tried to make up with Brown and later in the week claimed to be a sex addict, resulting in him attending a sex therapy session a week later where he claimed that he lost his virginity at eight years old to his sister, and had just slept with her two days ago. He was part of a storyline about him overcoming sex addiction, which he accomplished thanks to The Godfather.
After this twist, Henry turned into a fan favorite, and was seen on television romancing WWF veteran wrestler Mae Young as part of the "Sexual Chocolate" character. He feuded with Viscera during this time, as part of a storyline where Viscera splashed Mae Young while she was carrying Henry's child. Young later gave birth to a hand.
After a two year hiatus, Henry returned to the WWE in April 2002 and was sent to the SmackDown! brand, where he developed an in-ring persona of performing "tests of strength" while other wrestlers took bets on the tests, but the gimmick met with little success. During this time he competed against such superstars as Chris Jericho and Christian.
In August 2003, Henry returned to WWE television on the Raw roster as a heel where he found some success as a member of "Thuggin' And Buggin' Enterprises", a group of African Americans led by Theodore Long who worked a race angle in which they felt they were victims of racism and were being held down by the "white man". During that time, Henry was involved in a brief program with World Heavyweight Champion Goldberg when former champion, Triple H, put a bounty on Goldberg. This was followed by a brief rivalry with Shawn Michaels, before he engaged in a rivalry with Booker T. After defeating Booker T twice, once in a street fight and once in a six-man tag team match, he lost to Booker T at the Armageddon pay-per-view in December 2003.
After spending 2004 and most of 2005 rehabilitating from a triceps tear, Henry made his return to television during the December 30, episode of SmackDown!, as he interfered in a WWE Tag Team Championship match, joining with MNM (Joey Mercury, Johnny Nitro, and Melina), to help them defeat Rey Mysterio and Batista for the championship. A week later on SmackDown!, Henry got in a confrontation with the World Heavyweight Champion Batista, and went on to interfere in a steel cage match between MNM and the team of Mysterio and Batista, helping MNM to retain their titles. Henry then had another match with Batista at a live event where Batista received a severely torn triceps that required surgery, forcing him to vacate his title. On the January 10, 2006 episode of SmackDown!, Henry was involved in a battle royal for the vacant World Heavyweight Championship. He was finally eliminated by Kurt Angle, who won the title.
A week later, Henry received assistance from Daivari, who turned on Angle and announced that he was the manager of Henry. With Daivari at his side, Henry faced Angle for the World Heavyweight Championship at the 2006 Royal Rumble in January, losing when Angle hit him with a chair (without the referee seeing) and pinned him with a roll-up.
On the March 10 episode of SmackDown!, Henry interfered in a World Heavyweight Championship match between Angle and The Undertaker, attacking the latter when he was seconds from possibly winning the title. Henry then performed a diving splash on Undertaker, driving him through the announcer's table. Henry was then challenged to a casket match by Undertaker at WrestleMania 22. Henry vowed to defeat The Undertaker and end his undefeated streak at WrestleMania, but The Undertaker defeated him. Henry had a rematch against The Undertaker on the April 7 episode of SmackDown!. It ended in a no-contest when Daivari introduced his debuting client, The Great Khali. Khali went to the ring and attacked The Undertaker, starting a new feud and ending Henry's.
During the rest of April and May, Henry gained a pinfall victory over the World Heavyweight Champion Rey Mysterio in a non-title match. Henry entered the King of the Ring Tournament, and lost to Bobby Lashley in the first round. He later cost Kurt Angle his World Heavyweight Championship opportunity against Mysterio, when he jumped off the top rope and crushed Angle through a table. Henry was then challenged by Angle to face off at Judgment Day, Henry then sent a "message" to Angle by defeating Paul Burchill. At Judgment Day, Henry defeated Angle by countout. Although winning, Angle got his revenge after the match by hitting Henry with a chair and putting him through a table.
Henry later went on what was referred to as a "path of destruction", causing injuries to numerous superstars. Henry "took out" Chris Benoit and Paul Burchill on this path of destruction, and attacked Rey Mysterio and Chavo Guerrero. These events led up to a feud with the returning Batista, whom Henry had put out of action with a legitimate injury several months beforehand. When Batista returned he and Henry were scheduled to face one another at The Great American Bash in July. Weeks before that event, however, on the July 15, 2006 Saturday Night's Main Event XXXIII, Henry was involved in a six-man tag team match with King Booker and Finlay against Batista, Rey Mysterio, and Bobby Lashley. During the match, Henry was injured, canceling the scheduled match at The Great American Bash, as Henry needed surgery. Doctors later found that Henry completely tore his patella tendon off the bone and split his patella completely in two.
Henry returned on the May 11, 2007 episode of SmackDown!, after weeks of vignettes hyping his return. He attacked The Undertaker after a World Heavyweight Championship steel cage match with Batista, allowing Edge to take advantage of the situation and use his Money in the Bank contract. Henry then began a short feud with Kane, defeating him in a Lumberjack Match at One Night Stand. Shortly after, Henry made an open challenge to the SmackDown! locker room, which nobody ever accepted. In the coming weeks he faced various jobbers—wrestlers who consistently lose to make their opponents look stronger—and quickly defeated them all. On August 3, he claimed that nobody accepted the open challenge to step into the ring with him because of what he had done to The Undertaker, presenting footage of his assault on The Undertaker. The Undertaker responded over the following weeks, playing various mind games with Henry. Henry finally faced The Undertaker again at Unforgiven in September, losing to him after being given a Last Ride. Following an unscripted backstage interview, Henry burst into tears and fled from the arena. Two weeks later, Henry lost a rematch to The Undertaker after The Undertaker performed a chokeslam on Henry.
After a short hiatus, Henry returned to WWE programming on the October 23 episode of ECW, attacking Kane, along with The Great Khali and Big Daddy V. Henry then began teaming with Big Daddy V against Kane and CM Punk, and was briefly managed by Big Daddy V's manager, Matt Striker. At Armageddon, Henry and Big Daddy V defeated Kane and Punk. Before WrestleMania XXIV aired, Henry participated in a 24-man battle royal to determine the number one contender for the ECW Championship, but failed to win.
As part of the 2008 WWE Supplemental Draft, Henry was drafted to the ECW brand. At Night of Champions, Henry defeated Kane and Big Show in a Triple Threat match to capture the ECW Championship in his debut match as an ECW superstar. Upon winning the title, it was made exclusive to the ECW brand once again. Henry's title win came nearly a full decade after he was awarded the European Championship, which was back in 1999 and the only title he held in WWE. A few weeks later, Hall of Famer Tony Atlas returned to WWE to act as Henry's manager. Shortly after, ECW General Manager Theodore Long, unveiled a new, entirely platinum ECW Championship belt design. In August, Henry defended the title against Matt Hardy at SummerSlam after getting himself disqualified; however championships cannot change hands via disqualification, meaning that Henry retained the title. Henry later lost the title to Hardy at September's Unforgiven in the Championship Scramble match.
Henry attempted to regain the championship throughout the end of 2008, and had a match against Hardy at No Mercy, but failed as he was unsuccessful. Henry and Atlas then engaged in a scripted rivalry against Finlay and Hornswoggle, which included Henry losing a Belfast Brawl at Armageddon. At the start of 2009, Henry qualified for the Money in the Bank ladder match at WrestleMania XXV, and was involved in a series of matches with the other competitors on Raw, SmackDown, and ECW. He was unsuccessful at WrestleMania, however, as CM Punk won the match. In May, Henry began a rivalry with Evan Bourne, which began after Bourne defeated Henry by countout on the May 26 episode of ECW.
On June 29, Henry was traded to the Raw brand and redebuted for the brand that night as the third opponent in a three-on-one gauntlet match against WWE Champion Randy Orton, which he won, turning Henry into a face in the process. In August 2009, Henry formed a tag team with Montel Vontavious Porter and the two challenged the Unified WWE Tag Team Champions Jeri-Show (Chris Jericho and Big Show) for the title at Breaking Point, but were unsuccessful. They stopped teaming afterwards, becoming involved in separate storylines, until the February 15, 2010 episode of Raw in which they defeated the Unified WWE Tag Team Champions Big Show and The Miz in a non-title match. The next week they challenged The Big Show and The Miz in a title match but were unsuccessful. At Extreme Rules, Henry and MVP fought for a chance to become number one contenders to the Unified WWE Tag Team Championship, but were the second team eliminated in a gauntlet match by The Big Show and The Miz. Ultimately, The Hart Dynasty (Tyson Kidd and David Hart Smith) won the match.
Henry mentored Lucky Cannon in the second season of NXT. Cannon was eliminated on the August 10 episode of NXT. In September, Henry began teaming with Evan Bourne, starting at the Night of Champions pay-per-view, where they entered a Tag Team Turmoil for the WWE Tag Team Championship. They made it to the final two before being defeated by Cody Rhodes and Drew McIntyre. The team came to an end in October when Bourne suffered an injury and was taken out of action. Henry then formed a team with Yoshi Tatsu on the November 29 episode of Raw, defeating WWE Tag Team Champions Justin Gabriel and Heath Slater, after a distraction by John Cena. They received a shot at the championship the next week, in a fatal four-way elimination tag team match, which also included The Usos and Santino Marella and Vladimir Kozlov. Henry and Tatsu were the first team eliminated in the match.
On the April 25, 2011 episode of Raw, Henry was drafted back to SmackDown as part of the 2011 WWE draft. In the main event of the night, Henry attacked his teammates John Cena and Christian, turning heel in the process. On the May 27 episode of SmackDown, Henry participated in a Triple Threat match against Sheamus and Christian to decide the number one contender to the World Heavyweight Championship, which was won by Sheamus. On the June 17 episode of SmackDown, Henry was scheduled to face an angry and emotionally unstable Big Show, who warned Henry not to get into the ring; Henry ignored the warning and Big Show assaulted him before the match could begin. This act ignited a feud between the two; Henry attacked Big Show both backstage and during matches while on the July 1 episode of SmackDown, Big Show's music played during Henry's match against Randy Orton, causing Henry to be counted out and costing him a shot at the World Heavyweight Championship. Henry reacted by destroying the audio equipment and manhandling a technician. Henry faced Big Show in a singles match at Money in the Bank and won. After the match, Henry crushed Show's leg with a chair, (kayfabe) injuring him, an act Henry later referenced as an induction into the "Hall of Pain". Henry did the same to Kane on the next episode of SmackDown, and in the months ahead, Vladimir Kozlov and The Great Khali suffered the same fate.
On the July 29 episode of SmackDown, Henry was informed that he could no longer compete as no one dared to fight him, but Sheamus interrupted, saying that he wasn't afraid of Henry before slapping him. At SummerSlam, Henry defeated Sheamus by count-out after slamming him through a ring barricade. On the August 19 episode of SmackDown, Henry won a 20-man battle royal to become the number one contender for the World Heavyweight Championship to face Randy Orton at Night of Champions, and throughout weeks on SmackDown and Raw, Henry regularly attacked Orton, getting an advantage over him. At Night of Champions, Henry defeated Orton to become World Heavyweight Champion for the first time in his 15 years with WWE. Henry successfully defended the title against Orton at Hell in a Cell in a Hell in a Cell match.
On the October 7 episode of SmackDown, Big Show returned and chokeslammed Henry through the announce table, thus earning a title shot against Henry at Vengeance. During the match, Henry superplexed Big Show from the top rope, causing the ring to collapse from the impact and the match to be ruled a no contest. Henry began a feud with the Money in the Bank briefcase holder Daniel Bryan on the November 4 episode of SmackDown, challenging Bryan to a non-title match to prove that Bryan could not become champion. During the match, Big Show knocked out Henry, making him win by disqualification. Show then urged Bryan to cash in his contract, but Henry recovered and attacked both Bryan and Big Show before the match could start. At Survivor Series, Henry retained the World Heavyweight Championship against Big Show after a low blow that disqualified Henry. Angered by Henry's cowardice, Big Show crushed Henry's ankle with a steel chair. On November 25, Henry was knocked out again by Big Show, at which point Bryan cashed in his briefcase for a title match and quickly pinned Henry. However, SmackDown authority figure Theodore Long revealed that Henry was not medically cleared to compete and voided the match, so Henry remained champion and the briefcase was returned to Bryan. Later that night, Bryan won a fatal-four-way match to face Henry for the World Heavyweight Championship in a steel cage. On the November 29 of SmackDown, Henry defeated Bryan to retain his championship.
At TLC: Tables, Ladders & Chairs, Henry lost the World Heavyweight Championship to Big Show in a chairs match. After the match, Henry knocked Big Show out, resulting in Daniel Bryan cashing in his Money in the Bank to win his first World Heavyweight Championship. On the January 20 episode of SmackDown, Bryan retained the championship against Henry in a lumberjack match after Bryan provoked the lumberjacks to come in and attack them to cause a no contest. At the 2012 Royal Rumble event, Henry faced Bryan and Show in a triple threat steel cage match for the World Heavyweight Championship; Bryan escaped the cage to retain the title. On the February 3 episode of SmackDown, Henry was suspended indefinitely (in storyline) by SmackDown General Manager Theodore Long, after Henry physically accosted Long as he demanded a one-on-one rematch that night with Bryan. In reality, Henry had suffered a hyper-extended knee the previous week. Henry returned to in-ring action on the February 20 episode of Raw, losing to Sheamus. On the April 2 and 9 episodes of Raw, Henry faced CM Punk for the WWE Championship which he won by count-out and disqualification; as a result, Punk retained his title. On the April 16 episode of Raw, Punk defeated Henry in a no-disqualification, no count-out match to retain the WWE Championship. On May 14, Henry announced he was going under a career-threatening surgery for an injury.
After a nine-month absence, Henry made his return on the February 4, 2013 episode of Raw, brutally attacking Daniel Bryan, Rey Mysterio and Sin Cara. Four days later on SmackDown, Henry defeated Randy Orton to earn a spot in the number one contenders' Elimination Chamber match for the World Heavyweight Championship at Elimination Chamber. At the pay-per-view on February 17, Henry eliminated Daniel Bryan and Kane before being eliminated by Randy Orton. After his elimination, Henry attacked the three remaining participants before being escorted out by WWE officials. Henry then began a feud with Ryback after several non-verbal confrontations. On the March 15 episode of SmackDown, Henry was defeated by Ryback via disqualification, following interference from The Shield. Afterward, Henry delivered the World's Strongest Slam to Ryback three times in a row. On April 7 at WrestleMania 29, Henry defeated Ryback in a singles match. Later that month, Henry reignited a feud with Sheamus by repeatedly attacking Sheamus backstage. Henry and Sheamus then challenged each other in tests of strength, but with Sheamus unable to best Henry, he resorted to attacking Henry with Brogue Kicks. After Sheamus (during his match) Brogue Kicked Henry (who was on commentary), Henry snapped and brutally whipped Sheamus with a belt. This led to a strap match on May 19 at Extreme Rules, where Sheamus emerged victorious. With the loss to Sheamus, Henry declared that he was "going home".
After being absent from television due to injuries, Henry used social media to tease his retirement. On the June 17 episode of Raw, Henry returned, interrupting WWE Champion John Cena and delivering an emotional retirement speech, which was revealed as a ruse when Henry gave Cena a World's Strongest Slam after concluding his speech. With Henry stating his intent to challenge for the "only title he's never held", he was granted a WWE Championship match against Cena at Money in the Bank. On July 14 at the pay-per-view, Henry failed in his title challenge against Cena after submitting to the STF. The following night on Raw, Henry cut a promo to congratulate Cena on his win and asked for a rematch for SummerSlam, but was ultimately attacked by The Shield, turning face in the process for the first time since 2011. Henry continued his face turn the following week, by confronting The Shield and teaming together with The Usos to fend them off. Henry and the Usos went on to lose to The Shield in two six-man tag team matches, the first on the July 29 episode of Raw, and the second on the August 7 episode of Main Event. On the August 12 episode of Raw, Henry competed in a battle royal to determine the number one contender for the United States Championship, but was the last man eliminated by Rob Van Dam. After the match, Henry and Van Dam were confronted by The Shield, before the returning Big Show came to their aid. Four days later on SmackDown, Henry, Show, and Van Dam defeated The Shield in a six-man tag team match. After a suspected hamstring injury on August 31 at the TD Garden in Boston Massachusetts, Henry was cleared to compete. Henry, however, took time off and during his time off, he dropped down to 405 pounds and shaved his head bald.
Henry returned to in-ring action on November 24 at Survivor Series, answering Ryback's open challenge and defeating him. On the January 6, 2014 episode of Raw, Henry tried to confront Brock Lesnar during separate encounters after Lesnar's return, resulting in Henry receiving an F-5 the first time and then Lesnar injured Henry's arm after getting it in a kimura lock hold, causing Henry to wail in pain and be absent. He returned on February 10 episode of Raw, and answered Dean Ambrose's open challenge for the United States Championship, but was unable to win the title due to interference by the rest of The Shield. In March, Henry suffered another attack from Lesnar, this time resulting in Henry receiving an F-5 through the announcing table. On the August 4 episode of Raw, Henry defeated Damien Sandow after a few months absence. That same week on SmackDown, Henry formed a tag team with Big Show to defeat RybAxel (Ryback and Curtis Axel). On the August 18 episode of Raw, Henry entered a feud with Rusev by attacking him. This set up a match between Henry and Rusev at Night of Champions, which he lost by submission. The following night on Raw, he lost to Rusev again by knockout via submission. On the October 27 episode of Raw, Henry attacked Big Show during their tag team match against Gold and Stardust, and turning heel in the process. On the November 3 episode of Raw, Henry lost to Big Show via disqualification and slammed Big Show onto the steel steps. On the November 10 Raw, he joined The Authority's team to face John Cena's team at Survivor Series. On November 23 at Survivor Series, Henry was the first to be eliminated from Team Authority 50 seconds into the match after being knocked out by Big Show. Henry then took another hiatus due to an unspecified injury.
Henry returned on the March 12, 2015 episode of SmackDown, confronting Roman Reigns for having a lack of identity and for not being respected, resulting in Reigns attacking Henry. The attack caused Henry to become a believer in Reigns, and turning face in the process. Henry was unsuccessful in the Elimination Chamber match for the vacant Intercontinental Championship at Elimination Chamber, replacing Rusev who was injured, but was eliminated by Sheamus. On the Royal Rumble pre-show on January 24, 2016, Henry teamed with Jack Swagger to win a Fatal 4-Way tag team match to earn their spots in the Royal Rumble match. Despite this victory, Henry entered the Rumble match at #22 and lasted only 47 seconds when he was quickly eliminated by The Wyatt Family. At WrestleMania 32, Henry entered his third André the Giant Memorial Battle Royal, where he made it to the final six competitors until being eliminated by Kane and Darren Young.
On July 19, at the 2016 WWE draft, Henry was drafted to Raw. On the August 1 episode of Raw, Henry claimed he still "had a lot left in him" when he spoke of reviving the Hall of Pain. Raw General Manager Mick Foley gave Henry a United States Championship match, but Henry would lose by submission to Rusev. In October, Henry allied himself with R-Truth and Goldust in a feud against Titus O'Neil and The Shining Stars (Primo and Epico), in which Henry's team came out victorious. Henry returned at the Royal Rumble on January 29, 2017 as entrant number 6, only to be eliminated by Braun Strowman. He unsuccessfully competed in the Andre the Giant Memorial Battle Royal at WrestleMania 33.
Following WrestleMania 33, Henry retired and transitioned into a backstage producers role. He later made his return in a backstage cameo at the Raw 25 Years event in January 2018. On March 19, 2018, it was announced that Henry would be inducted into the WWE Hall of Fame. On April 27, at the Greatest Royal Rumble, Henry participated in the event's Royal Rumble match, scoring 3 eliminations, but was himself eliminated by Daniel Bryan and Dolph Ziggler.