Kennedy made his first appearance for the World Wrestling Federation on Jakked in 2001, where he lost to Essa Rios.
Kennedy, as a heel, defeated Funaki in his SmackDown! debut on August 25, 2005. Kennedy also created an ongoing mini-feud with SmackDown! ring announcer Tony Chimel, based on Kennedy believing that Chimel's announcing was not done well enough or with sufficient respect, and therefore performing his own introductions or forcing Chimel to introduce him again. Kennedy's self-ring introductions before the match became one of his trademarks. Kennedy made his pay-per-view debut at No Mercy, defeating Hardcore Holly and injuring Holly's ribs during the match.
On the November 11 episode of SmackDown!, Kennedy faced Eddie Guerrero to compete for a spot on SmackDown!'s Survivor Series team. He lost the match when Guerrero tossed him a steel chair and played possum, a move which Guerrero had made famous. The referee turned around and saw Guerrero on the ground with Kennedy holding the chair, and consequently disqualified Kennedy, awarding the place on Team SmackDown! to Guerrero. This was Kennedy's first loss. In retaliation, Kennedy struck Guerrero over the head with the chair after the match. This was Guerrero's final televised match, as he died two days later.
In December, Kennedy participated in WWE's overseas tour. On the second day in Italy, Kennedy suffered a legitimate latissimus dorsi tear. Kennedy was sidelined for nearly six months while he rehabilitated the injury. He continued to make appearances on SmackDown! and Velocity throughout January and February and even made an appearance on the January 11, 2006, episode of WWE Byte This! with Todd Grisham to maintain visibility.
Kennedy made his return to SmackDown! on the June 9 episode with a victory over Scotty 2 Hotty after using the Kenton Bomb. On the July 14 episode of SmackDown!, Matt Hardy used a roll-up to defeat Kennedy, ending Kennedy's streak of never being defeated by pin or submission. On the July 21 episode of SmackDown!, Batista put out an open challenge to find an opponent for The Great American Bash, as his original opponent, Mark Henry, had been injured. Kennedy accepted the challenge and won the match by disqualification, however, he suffered a injury during the match after being thrown headfirst into the steel steps, resulting in an exposed cranium laceration which required twenty stitches to close. Kennedy helped Vince and Shane McMahon in their feud with D-Generation X, appearing at both SummerSlam and the August 28 episode of Raw to attack them.
On the September 1 episode of SmackDown!, Kennedy defeated Finlay and Bobby Lashley in a triple threat match to win the WWE United States Championship, his first and only championship reign in WWE. On the September 8 episode of SmackDown!, Kennedy announced that he wanted to move over to the Raw brand, as SmackDown! did not interest him anymore since he had already defeated every top performer on the roster. This led to SmackDown! General Manager Theodore Long making a match between Kennedy and The Undertaker, who Kennedy had never faced, to be held at No Mercy. Kennedy won the match by disqualification. On the October 13 episode of SmackDown!, Kennedy, now with a win over The Undertaker, again stated his desire to move to Raw. However, Long again put him against an opponent who he had never faced—this time Chris Benoit—with Kennedy's title on the line. Long said that if Kennedy were to defeat Benoit, he would be given his release and be allowed to go to Raw. Ultimately, Kennedy lost the match and the United States Championship to Benoit after submitting to the Crippler Crossface following a distraction by The Undertaker.
In November, Kennedy joined forces with Montel Vontavious Porter (MVP) in matches against The Brothers of Destruction (Undertaker and Kane). On the November 3 episode of SmackDown!, Kennedy and MVP lost to the Brothers of Destruction three times. After first getting counted out, Theodore Long restarted the match with no countouts. When Kennedy disqualified his team by performing a low blow, Long restarted the match again with no countouts and no disqualifications. Kennedy and MVP continued to feud with the two, with MVP feuding with Kane while Kennedy challenged the Undertaker to a match at Survivor Series, which was later announced as a First Blood match. Kennedy won the match after MVP turned on him and aimed for his head with a steel chair, but missed and hit the Undertaker instead, leaving him bleeding. After the match, the Undertaker attacked Kennedy, forcing him to bleed. At Armageddon, Kennedy and the Undertaker met in a final match; they were scheduled in a Last Ride match. In the match, the Undertaker defeated Kennedy.
After a brief hiatus, Kennedy returned to SmackDown! on January 5, 2007, and defeated Chris Benoit in a "Beat the Clock" match, with the overall prize being a shot at Batista's World Heavyweight Championship at the Royal Rumble. After he prevented The Undertaker from beating his time, Kennedy's time of 5:07 ended up being the fastest. At the Royal Rumble, he lost the match, as well as a subsequent rematch on the February 9 episode of SmackDown!. From there, Kennedy began a short feud with ECW World Champion Bobby Lashley, leading to a match at No Way Out for the title, which Kennedy won by disqualification. Kennedy challenged Lashley unsuccessfully on the February 20 episode of ECW and the March 2 episode of SmackDown! as well.
Kennedy earned a spot in the 2007 Money in the Bank ladder match by defeating Sabu in an Extreme Rules match on the February 27 episode of ECW. At WrestleMania 23, Kennedy won the Money in the Bank ladder match, giving him the right to challenge any world champion in WWE at any date up until WrestleMania XXIV. Kennedy announced on the April 30 episode of Raw that he would be cashing in his Money in the Bank championship opportunity in eleven months at WrestleMania XXIV. On the May 7 episode of Raw, Kennedy, however, lost his Money in the Bank briefcase to Edge, losing moments after being struck with a monitor before the match began. Because of the injury Kennedy sustained during his match with Edge, it was revealed that his right triceps muscle tore off the bone and he would be out for a minimum of five to seven months. The injury, however, was not as serious as initially reported, as the triceps tendon did not tear off the bone but was, in fact, a massive hematoma.
On the June 11 episode of Raw, Kennedy was drafted to the Raw brand as part of the WWE Draft. On the August 20 episode of Raw, Carlito hosted the interview segment Carlito's Cabana. During the segment, Carlito challenged his guest, Umaga, for his Intercontinental Championship at SummerSlam, and Kennedy also demanded a shot at the title. Raw General Manager William Regal, scheduled a match between Kennedy and Carlito, in which the winner would receive an opportunity to face off against Umaga at SummerSlam. After the match ended in a draw, Regal booked a triple threat match at SummerSlam between the three men for the Intercontinental Championship; at the event, Umaga retained the title. On the September 10 episode of Raw, Mr. McMahon revealed that Kennedy had, in storyline, been suspended for "impersonating a McMahon."
After his suspension, Kennedy returned to television on the October 1 episode of Raw, facing John Cena in the main event and losing. At No Mercy, Kennedy took part in a six-man tag team match alongside World Tag Team Champions Lance Cade and Trevor Murdoch, defeating Paul London, Brian Kendrick and Intercontinental Champion Jeff Hardy. For several weeks, Kennedy began a feud with Hardy, which consisted of the two facing off in a singles match and numerous tag team matches, most of which Hardy won. At Cyber Sunday, Kennedy and Hardy were two of the eligible wrestlers that could earn a WWE Championship match that evening, pending a fan votes. Neither man won the opportunity, as Shawn Michaels won the vote and earned a shot at the title.
Kennedy next entered a feud with Michaels on the night after Survivor Series. Kennedy claimed that it was time for Michaels to move on and let the younger wrestlers achieve success. At Armageddon, Michaels defeated Kennedy by executing Sweet Chin Music. On the December 31 episode of Raw, Kennedy pinned Michaels in a rematch by executing his new finishing move, the Mic Check. In subsequent rematches, the two traded wins over each other.
After several months of minor feuds and short storylines, Kennedy was not seen for weeks after WrestleMania XXIV because he was filming Behind Enemy Lines: Colombia. Kennedy returned to Raw on April 28, 2008, confronting and brawling with Raw General Manager and newly-crowned King of the Ring William Regal, turning face in the process. On the May 19 episode of Raw, Kennedy defeated Regal in a "Loser Gets Fired match", thereby opening up the General Manager spot on the Raw brand.
During the WWE Draft on June 23 on Raw, Kennedy was drafted back to the SmackDown brand. On August 4, he dislocated his shoulder in a match against Shelton Benjamin at a house show, keeping him off television for three months. Kennedy made his return to WWE television, in a non-wrestling capacity, on the November 24 episode of Raw, promoting Behind Enemy Lines: Colombia.
On April 15, 2009, Mr. Kennedy was drafted back to Raw as the brand's first pick of the 2009 Supplemental Draft. On the May 11 episode of Raw, WWE aired a video package to promote Kennedy's return. He made his official Raw return two weeks later, competing in a 10-man tag team match, which his team won.
Kennedy was released from his WWE contract on May 29, just four days after his return.