In May 2003, Carlito wrestled in two tryout matches for World Wrestling Entertainment. His opponents were Tommy Dreamer and Jamie Noble, with both contests ending in a loss.
On October 14, 2003, he teamed with Simon Dean in a dark match loss to Sean O'Haire and Matt Morgan that preceded WWE Velocity. Throughout March and May 2004, Carlito wrestled in dark matches for both the Raw and SmackDown! brands. The outcome of these unofficial presentations were wins over Paul London, Ruffy Silverstein, Wavell Starr and Ricky Reyes, also including losses to Hardcore Holly, Funaki, Shannon Moore and Billy Kidman.
On June 7, 2004, Carlito wrestled in a dark match, this time losing to Sean Morley. On September 19, 2004, he wrestled under the name of Carlito Caribbean Cool on a SmackDown! house show and defeated Scotty 2 Hotty.
On October 7, 2004, he made his debut as a heel on SmackDown! as "Carlito Caribbean Cool" (though later shortened to simply Carlito), whose gimmick was an apple toting big mouth who would spit apple "in the face of people who don't want to be cool". Carlito defeated John Cena for the United States Championship in his first match on the main roster by using a steel chain to knock out Cena. He immediately entered an undefeated streak of 14 contests, during which he successfully defended the title against Rob Van Dam, Rey Mysterio, Eddie Guerrero and Hardcore Holly, also defeating Shannon Moore in a non-title match. Carlito was then involved in a storyline where his bodyguard Jesús stabbed Cena in a nightclub. Carlito held the United States Championship for forty-two days, losing it back to Cena after suffering a legitimate injury. Carlito made his pay-per-view debut at the 2004 Survivor Series, where he represented Team Angle in an eight-man tag team match against Team Guerrero, but did not actually participate in the event after being chased out of the building by Cena.
While Carlito was recovering from an injury, he was involved in a comical angle with SmackDown!'s general manager, Theodore Long. The storyline consisted of Carlito being forced to do demeaning chores around the arena, such as selling hot dogs, removing snow from parking lots with a shovel and mopping floors. As a result of these actions, Carlito created a petition in support of Long's destitution, but was unsuccessful. Carlito made his WrestleMania debut in a non-wrestling role at WrestleMania 21, in which he interrupted an edition of Rowdy Roddy Piper's Piper's Pit, with Stone Cold Steve Austin as the special guest. Following WrestleMania, Carlito created an interview segment entitled Carlito's Cabana. Carlito then entered a feud with The Big Show after a spot where Show refused an offer to work in an enforcer role for Carlito. This feud involved Carlito tricking Show into eating a poisoned apple, and Matt Morgan becoming Carlito's enforcer. This feud ended with Carlito defeating Show at Judgment Day.
Carlito was drafted to the Raw brand in the 2005 WWE Draft Lottery, where he defeated Shelton Benjamin for the Intercontinental Championship in his debut match for the brand. He then lost the Intercontinental title to Ric Flair at Unforgiven. Towards the end of 2005, Carlito was involved in a brand rivalry which led to him discontinuing Carlito's Cabana. The angle concluded with Carlito wrestling for Team Raw against Team SmackDown! in a Survivor Series match at the Survivor Series.
In late 2005, Carlito was added to angles involving the WWE Championship. After defeating Shelton Benjamin in a qualifying match, Carlito was added to the main event at New Year's Revolution in early 2006, the Elimination Chamber match. He was one of the final two wrestlers remaining, after eliminating Kane, Chris Masters and Shawn Michaels. He then lost the match to John Cena. Following New Year's Revolution, Carlito and Chris Masters joined forces as a tag team. Together, they competed against Big Show and Kane for the World Tag Team Championship at WrestleMania 22. Carlito and Masters lost when Masters accidentally attacked Carlito. Following the match, Carlito confronted Masters, igniting a feud between them. Carlito turned face when he attacked Chris Masters after his "Masterlock Challenge" the next night on Raw. This storyline came to a conclusion at Backlash, where Carlito defeated Masters via an illegal assist from the ropes.
At Vengeance, Carlito fought in a triple threat match against Shelton Benjamin and Johnny Nitro for Benjamin's Intercontinental title. Nitro won the match after pulling Carlito outside of the ring and pinning him. Following Vengeance, Carlito began an on-screen relationship with Trish Stratus. He also engaged in a short feud with Johnny Nitro and Melina, which ended after Carlito and Stratus defeated Nitro and Melina in a mixed tag team match at Saturday Night's Main Event XXXIII. Carlito next feuded with Randy Orton, following a spot where Orton attempted to attack Stratus during a backstage segment. The two wrestlers were booked for a match at Unforgiven and a rematch on Raw; Orton won both matches. The feud concluded in a match at WWE's annual Tribute to the Troops event, where Carlito won by pinfall. The angle involving Carlito's relationship with Trish Stratus lasted until Stratus' retirement from wrestling following Unforgiven.
In the final months of 2006, Carlito competed in several matches involving the Intercontinental Championship. His involvement in this angle ended at Cyber Sunday, after being elected by the fans to face Jeff Hardy for the championship. Carlito, however, lost the match. During this time period, Carlito's gimmick underwent a slight change and was sold as a "ladies man", eventually getting involved in another fictional relationship with Torrie Wilson. Carlito participated in the 2007 Royal Rumble, where he was eliminated by The Great Khali. Following the Royal Rumble, Carlito started a feud with Ric Flair, in which Flair insulted Carlito for leaving a show early by claiming that he had no heart, no passion and was undeserving of his spot on the roster. After Carlito challenged and lost to Flair in a match, they were booked as a tag team, with Flair serving as a mentor to Carlito. The team was involved in a Money in the Bank qualifying match which was declared a "no contest" after The Great Khali interfered. This led to a triple threat match the following week which included and was won by Randy Orton.
Carlito participated in a dark match at WrestleMania 23, winning in a tag team match with Flair as his partner against the team of Chavo Guerrero and Gregory Helms. The team also lost a number one contender's match for the World Tag Team Championship against Lance Cade and Trevor Murdoch. Carlito turned on Flair after the loss, which turned him heel again. Their feud ended with a match at Judgment Day, where Carlito lost to Flair by submission.
Following his feud with Flair, he was involved in angles with The Sandman and Triple H. He then lost to Triple H at Unforgiven in a no disqualification match where the no disqualification rule only applied to Carlito. On December 10, 2007, he was featured in a ladder match at the Raw 15th Anniversary against Jeff Hardy for the Intercontinental Championship, which Hardy won. Carlito defeated Cody Rhodes to qualify for the Money in the Bank ladder match at WrestleMania XXIV. He failed to win at the event. Carlito then formed a tag team with Santino Marella. The team was placed in several matches involving the World Tag Team Championship, twice being named the number one contenders; however, they lost the relevant championship matches.
As part of the 2008 WWE Supplemental Draft, Carlito was drafted back to the SmackDown brand. On September 12, he re-debuted on the brand turning face, forming a tag team with his brother, Primo. They defeated WWE Tag Team Champions Curt Hawkins and Zack Ryder in the match to gain their first victory as a team. Two weeks later, both teams competed in a title match, with The Colóns winning to become tag team champions. Subsequently, Carlito and Primo entered a feud with World Tag Team Champions John Morrison and The Miz. At WrestleMania XXV, The Colóns defeated Miz and Morrison in a tag team unification match, becoming the first team to simultaneously hold both sets of the company's Tag Team Championships since their creation.
On April 15, 2009, both Carlito and Primo were drafted back to the Raw brand as part of the 2009 Supplemental Draft. At The Bash, the duo dropped the Unified Tag Team Titles to Edge and Chris Jericho in a triple threat tag team match also involving Ted DiBiase and Cody Rhodes. Carlito and Primo invoked their rematch clause the next night on Raw, but were unsuccessful.
On the July 6 episode of Raw, following their loss to Edge and Jericho, Carlito turned heel by attacking Primo. At Night of Champions, Carlito challenged for the United States Championship in a Six-Pack Challenge, which also involved Primo, but neither of them were able to win the title. On the August 3 episode of Raw, Carlito defeated Primo to end their feud. On the August 13 episode of WWE Superstars, Carlito teamed with Rosa Mendes to defeat Kofi Kingston and Mickie James. Mendes would then become Carlito's manager until she was traded to the ECW brand in September.
After a two-month hiatus, on the November 30 episode of Raw, Carlito returned to confront John Cena, after Cena challenged Sheamus to come out to the ring, telling him everyone on the roster were tired of him and that Sheamus was their representative of what the roster believed and then tried to spit apple in Cena's face, which led to him getting hit with Cena's finisher, the Attitude Adjustment. The following week, Carlito was defeated by Cena.
On the January 25, 2010 edition of Raw, Carlito was booked to face Kelly Kelly in an intergender singles match. However, before the match was able to start, Santino Marella entered the ring and was attacked by Jack Swagger. Six days later, Carlito took part in the Royal Rumble, entering fifteenth, but was eliminated by Shawn Michaels.
In February 2010, Carlito was announced as one of the eight WWE Pros for the first season of WWE NXT. On the February 22 episode of Raw, Carlito was defeated by Christian in a Money in the Bank qualifying match. The next night on WWE NXT, Carlito teamed with his NXT rookie Michael Tarver in a losing effort against Christian and his NXT rookie Heath Slater. On the May 6 episode of WWE Superstars, during his match with Primo, Carlito would stop the match and told Primo they shouldn't fight. Primo would agree and reunite with his brother, turning heel in the process. On the May 10 episode of Raw, Carlito and Primo attacked R-Truth for Ted DiBiase, who paid them afterwards. On May 21, Carlito was released due to a violation of the WWE Wellness Program.
In March 2014, his father Carlos Colón was announced as a WWE Hall of Fame inductee as part of the 2014 class. On April 6, 2014, Carlito joined the other members of the family during the official induction ceremony.
Carlito made a surprise appearance during the 2021 Royal Rumble match as the eighth entrant, and lasted eight minutes before being eliminated by Elias. On the February 1 episode of Raw, Carlito teamed up with Jeff Hardy in his first match on Raw in ten years, defeating Elias and Jaxson Ryker.
At Backlash 2023, Carlito interfered during the San Juan Street Fight between Bad Bunny and Damian Priest, helping Bunny defeat Priest as an associate of the Latino World Order (LWO). Months later in October at Fastlane, Carlito returned to team up with the LWO's Rey Mysterio and Santos Escobar to defeat Bobby Lashley and The Street Profits in a six-man tag team match. On the November 10 episode of SmackDown, Carlito accused Escobar of purposefully leaving brass knuckles inside the ring at Crown Jewel, which cost Mysterio the United States Championship to Logan Paul. After Carlito's match with Bobby Lashley on the November 10 SmackDown, Escobar turned heel and assaulted Mysterio, who was checking on Carlito. A match between Carlito and Escobar was then announced for Survivor Series WarGames the following week. A day before the event, however, Escobar took out Carlito in the ring and backstage. Dragon Lee would save Carlito from Escobar and SmackDown General Manager Nick Aldis allowed Lee to face Escobar as Carlito's replacement at Survivor Series WarGames. At the event, Lee lost the match. On January 2, 2024, at NXT New Year's Evil, Carlito returned as the third partner (replacing Lee, who was originally in the match but had to miss the event due to travel issues) to LWO's Joaquin Wilde and Cruz Del Toro and defeated The No Quarter Catch Crew (Drew Gulak, Myles Borne, and Damon Kemp) in a six-man tag team match. Carlito entered the Royal Rumble match at the titular event as the tenth entrant, where he eliminated Santos Escobar before being eliminated by Bobby Lashley.
On the March 29 episode of SmackDown, Rey and Dragon Lee, the newest member of the LWO, challenged Escobar and "Dirty" Dominik Mysterio to a tag team match at WrestleMania XL, however Lee was attacked backstage, rendering him unable to compete at WrestleMania. On the April 26 episode of SmackDown, it was revealed that Carlito was behind the attack on Lee, turning heel and leaving the LWO. During night two of the WWE Draft, Carlito was drafted to Raw with the rest of the LWO, despite leaving the group.
Following being drafted to Raw, Carlito began to insert himself into The Judgment Day, but was kept at arm's length by Damian Priest, citing their past conflict. On the May 13 episode of Raw, Carlito helped Finn Bálor and JD McDonagh win a fatal four-way match to become the number one contenders for the World Tag Team Championships. One week later, Bálor and McDonagh failed to win the titles from The Awesome Truth (The Miz and R-Truth) after Braun Strowman prevented Carlito from interfering. On the August 5 episode of Raw, Carlito became an official member of The Judgment Day, after Priest and Rhea Ripley were both kicked out of the group following SummerSlam.