O'Neil competed in the second season of WWE NXT, with Zack Ryder as his mentor. He debuted on June 8, 2010, teaming with Ryder to lose to John Morrison and Eli Cottonwood. During and after the bout the two argued. The following week the two made up. Two weeks later, O'Neil was the first person eliminated from the second season of NXT, and gave a farewell speech before leaving the arena. O'Neil returned for the season finale on August 31, joining the other eliminated rookies in attacking the winner, Kaval.
In March 2011, O'Neil was selected as one of the six former NXT contestants to return to the show in its fifth season, NXT Redemption, being mentored by Hornswoggle. In the season premiere, O'Neil defeated Lucky Cannon in the main event. The two also feuded with Darren Young and his pro, Hornswoggle's old nemesis, Chavo Guerrero. Following Lucky Cannon's elimination on the May 14, 2011, episode of NXT Redemption, O'Neil lead the fans in a rendition of Na Na Hey Hey Kiss Him Goodbye, as a tribute to the recently retired Edge. On the June 21 episode of NXT Redemption, O'Neil's pro from season two, Zack Ryder, returned for one night only to face and defeat O'Neil. On the July 12, 2011, episode of NXT, he faced off against Darren Young and Derrick Bateman in a triple threat elimination match, which saw him lose to Bateman. 8 days later, O'Neil teamed up with NXT host Matt Striker in a winning effort against Darren Young and Derrick Bateman after Young was pinned by O'Neil.
On the September 8 episode of WWE Superstars, O'Neil teamed with Percy Watson in a losing effort against Curt Hawkins and Tyler Reks. O'Neil and Watson defeated Derrick Bateman and Tyson Kidd, as well as Bateman and JTG, but lost to Darren Young and JTG.
On the November 16, 2011, episode of NXT, O'Neil was assaulted by a returning Darren Young. Young was then able to get the better of O'Neil twice in tag team matches. The conclusion to O'Neil's feud with Young came when O'Neil defeated Young in a no disqualifications match on the January 18 episode of NXT. O'Neil then turned heel after the match, verbally ripping on the audience, his former pro Hornswoggle, and NXT itself.
O'Neil later urged his friend Percy Watson to also turn his back on the fans on the January 25, 2012, episode of NXT. When Watson refused, O'Neil shoved him and a match between the two was booked, leading to O'Neil defeating Watson. O'Neil continued to attack Watson after the match, leading to Alex Riley saving Watson. O'Neil then formed an alliance with former enemy Darren Young, and the duo teamed up to defeat Watson and Riley on the February 1 and 29 episodes of NXT. O'Neil also faced and defeated Riley on the February 22 episode of NXT. On the March 7 episode of NXT, O'Neil faced Watson, which would result in a loss for O'Neil. O'Neil and Young then moved on to feud with The Usos.
On the April 18 episode of NXT, it was announced that O'Neil, along with Darren Young, had been moved to the main roster. The team made their debut on the April 20 episode of SmackDown with a victory over The Usos. They began a winning streak before their streak was ended on the May 18 episode of SmackDown by WWE Tag Team Champions Kofi Kingston and R-Truth.
At the No Way Out pay-per-view, O'Neil and Young won a fatal-four way tag team match to become #1 contenders for the WWE Tag Team Championship after A.W. turned on his clients Primo & Epico. On the July 16 episode of Raw, O'Neil and Young unsuccessfully challenged Kofi Kingston and R-Truth for the WWE Tag Team Championship. On the August 10 episode of SmackDown, they defeated Primo & Epico in a #1 contenders match by disqualification when A.W. provoked Kingston and R-Truth, who were on commentary, into interfering in the match. That same day, A.W. was released from his contract. Despite losing A.W, the Prime Time Players received a title shot at SummerSlam, but were again defeated by Kingston and R-Truth. On the September 7 episode of SmackDown, The Prime Time Players defeated Primo and Epico and The Usos in a triple threat tag team match to earn another shot at the title. On Raw three days later, the Prime Time Players lost their title shot to the team of Kane and Daniel Bryan. At Survivor Series, O'Neil took part in a 10-man elimination tag team match, but was eliminated by Tyson Kidd.
At the 2013 Royal Rumble, O'Neil entered the Royal Rumble match at number 7 but was eliminated by Sheamus. On the March 18 episode of Raw, O'Neil played a new character called Rufus "Pancake" Patterson, his "uncle", accompanying Darren Young in his match against John Cena, in which Young was defeated.
On the August 19, 2013, episode of Raw, the Prime Time Players turned face in a winning effort against The Real Americans (Antonio Cesaro and Jack Swagger). On the Night of Champions pre-show, O'Neil and Young won a tag team turmoil upon entering last, for the opportunity to face The Shield for the WWE Tag Team Championship but lost to Seth Rollins and Roman Reigns on the pay-per-view. Furthering their face turn, the duo were amongst those who saved Daniel Bryan from being injured by Randy Orton. The Prime Time Players would be forced into a 3 on 1 handicap gauntlet match against The Shield as ordered by the COO, Triple H, the same as Dolph Ziggler, Kofi Kingston and Rob Van Dam.
On the January 31, 2014, episode of SmackDown, O'Neil allowed Curtis Axel to pin Young during a tag-team match. After the match, O'Neil attacked Young to turn heel and disbanded the Prime Time Players. O'Neil defeated Young at Elimination Chamber.
O'Neil lost a rematch to Young on the February 26 episode of Main Event. Following this loss, O'Neil began a losing streak to the likes of Big Show, Sheamus and Dolph Ziggler. From mid-April to mid-June, O'Neil commonly appeared on Superstars, where he suffered many losses to Kofi Kingston and Big E. He was also unsuccessful in winning four battle royals: the André the Giant Memorial Battle Royal at WrestleMania XXX, a battle royal for the WWE United States Championship in May, a Money in the Bank qualifying battle royal in June and a battle royal for the WWE Intercontinental Championship at Battleground.
In July, O'Neil formed a tag team with Heath Slater, later known as Slater-Gator. In July and August, they wrestled on Main Event and Superstars. Despite wins over the likes of Zack Ryder and Sin Cara and Gold and Stardust, they suffered losses to El Torito and Hornswoggle and Big E and Kofi Kingston. In September, Slater-Gator lost multiple matches to Adam Rose and to the team of Rose and The Bunny. O'Neil entered the Royal Rumble, being eliminated by Dean Ambrose and eventual winner Roman Reigns in 4 seconds.
On the February 16 episode of Raw, O'Neil turned face by saving his former tag team partner Darren Young from an attack from The Ascension, disbanding Slater-Gator. To acknowledge this breakup, Slater announced on social media that he is going to 'focus on himself'. Then on the February 23 episode of Raw, The Prime Time Players officially reunited to battle The Ascension, with Young picking up the victory. O'Neil participated in the 2nd Annual André the Giant Memorial Battle Royal at WrestleMania 31, before being eliminated by Ryback. At Elimination Chamber, the Prime Time Players participated in the first ever tag team Elimination Chamber match for the WWE Tag Team Championship, however they were the last team to be eliminated by the winners and defending champions The New Day (Big E, Kofi Kingston and Xavier Woods). At Money in the Bank, O'Neil and Young defeated The New Day to win the Tag Team Championship, their first titles in WWE. They later defeated The New Day in a rematch at Battleground. The Prime Time Players dropped the WWE Tag Team Championships back to The New Day at SummerSlam in a fatal–four way match, also involving The Lucha Dragons and Los Matadores. O'Neil and Young would invoke their championship rematch clause for the September 14 episode of Raw, which they ended up losing against New Day.
On the November 9 episode of Raw, O'Neil would enter the 16-man tournament to crown the new WWE World Heavyweight Champion, losing to Kevin Owens in the first round. On the Survivor Series kick-off show, O'Neil participated in a five-on-five elimination tag team match, teaming with The Dudley Boyz, Neville and Goldust to defeat Stardust, The Ascension, The Miz and Bo Dallas. On the February 8, 2016, episode of Raw, O'Neil had what was described as a "playful, physical" altercation with Vince McMahon as the show was going off the air while the two were on stage during Daniel Bryan's retirement celebration. The following day, O'Neil was suspended for unprofessional conduct relating to the incident, with the suspension reportedly lasting up to 90 days. It was later confirmed that he would be suspended for 60 days.
On the May 2 episode of Raw, O'Neil returned from suspension, participating in a battle royal to determine the #1 contender to the WWE United States Championship. On the May 26 episode of SmackDown, O'Neil entered a feud with United States Champion Rusev. This set up a match between O'Neil and Rusev for the United States Championship at Money in the Bank, which he lost. After the match, Rusev taunted and disrespected O'Neil's children. The following night on Raw, a rematch was scheduled but O'Neil attacked Rusev before the match began. On the July 4 episode of Raw, O'Neil lost in another title match to Rusev, ending the feud.
On July 19 at the 2016 WWE draft, O'Neil was drafted to Raw. On the August 1 episode of Raw, O'Neil started a slow heel turn when he questioned his former tag team partner Darren Young on his motives on being "great again". Later that night, he defeated Young by pinning him while grabbing Young's tights. Afterwards, O'Neil got into a backstage altercation with Young's manager Bob Backlund, ending in Young coming to Backlund's defense by attacking O'Neil. The week after on Raw, Young defeated O'Neil by pinning him while grabbing O'Neil's tights, mimicking the way O'Neil defeated him. On the August 15 episode of Raw, O'Neil and Young reconciled and were placed in a match against The Shining Stars. During the match, O'Neil attacked Young with a Clash of the Titus, cementing O'Neil's heel turn. Starting from September 2016, he began a losing streak whilst debuting a new gimmick known as "The Titus Brand". On the October 31 episode of Raw, O'Neil competed in a battle royal to determine who would join Team Raw at the upcoming Survivor Series pay-per-view against Team SmackDown, but was eliminated by Sami Zayn.
In April 2017, Apollo Crews caught the attention of O'Neil's new "Titus Brand" after being drafted to Raw and recruited him on the brand. He later recruited cruiserweight Akira Tozawa to his brand, which he renamed to "Titus Worldwide" and turned him face in the process. After Dana Brooke challenged Asuka to a match on the November 27, 2017, episode on Raw, in which she lost, O'Neil recruited Brooke to join the brand. Brooke made her first official appearance with the team on the January 1, 2018, episode of Raw accompanying Crews along with O'Neil in a match against Bray Wyatt, in which he was defeated and at this point Tozawa quietly left the team. On the January 8, 2018 episode of Raw, O'Neil and Crews defeated Cesaro and Sheamus in an upset win. On the January 29 episode of Raw, Crews and O'Neil competed in a match against Cesaro and Sheamus for their Tag Team Championships, in which they were unsuccessful at capturing the titles. On February 25 at Elimination Chamber, they competed in another match for the Raw Tag Team Championships, in a losing effort. On Raw the next night, Cesaro and Sheamus defeated Titus Worldwide in a 2 out of 3 falls match to retain the title, winning 2-0 to end the feud. O'Neil later participated in the André the Giant Memorial Battle Royal on the WrestleMania 34 kickoff show, but he was unsuccessful in both matches. He was also part of the 50-man Greatest Royal Rumble event in which he was eliminated by Braun Strowman. While running to the ring to participate in this match, he famously tripped and slid underneath the ring, which led to several internet memes and reactions from fellow superstars. A couple of days later on Raw during a match between Baron Corbin and No Way Jose, O'Neil would try to amend for that mistake, but as he entered the ring, he slipped and fell from the apron. On the September 3 episode of Raw, Dana Brooke parted ways with Titus Worldwide after a mid-match coaching backfired, causing Brooke and Ember Moon to lose to Bayley and Sasha Banks. On the October 15 episode of Raw, Crews, without O'Neil, returned as a singles competitor, thus disbanding Titus Worldwide.
On the November 2 episode of Main Event, O'Neil returned to singles competition, defeating Mojo Rawley. On January 27, 2019, at the Royal Rumble, O'Neil entered the Royal Rumble match at No. 11, but only lasted five seconds as he was quickly eliminated by Curt Hawkins. At WrestleMania 35 in April, O'Neil competed in the André the Giant Memorial Battle Royal, which he failed to win. On the May 20 episode of Raw, O'Neil became the inaugural holder of the 24/7 Championship. His reign ended in less than a minute when Robert Roode pinned him.
On the October 19, 2020 episode of Raw, O'Neil attempted to join MVP's The Hurt Business stable, only to be rejected and assaulted. On the November 9, 2020 episode of Raw, he challenged Bobby Lashley for the United States Championship, but was unsuccessful in capturing the title. In March 2021, O'Neil was announced as a co-host for WrestleMania 37, alongside Hulk Hogan. Later that month, O'Neil was announced as the recipient of the Warrior Award for the 2020 class of the WWE Hall of Fame, to be inducted alongside the 2021 class.