Tajiri debuted on the May 24, 2001 episode of SmackDown! as a face and was given the gimmick of WWF Commissioner William Regal's assistant. With the help of Regal, Tajiri made his in ring debut against Crash in a King of the Ring 2001 qualifying match which Tajiri won, he was later eliminated by Rhyno. Tajiri would win his first championship in WWF by defeating Alliance member X-Pac for the WWF Light Heavyweight Championship on an episode of Raw is War. X-Pac would quickly capture the Cruiserweight Championship and at SummerSlam 2001 Tajiri would lose a championship unification match therefore retiring the Light Heavyweight Championship. Tajiri would quickly bounce back as he began an on-screen relationship with Torrie Wilson and defeated Chris Kanyon for the United States Championship. However, Tajiri would lose the belt to Rhyno soon afterwards at Unforgiven in September. After Regal turned heel by joining The Alliance, Tajiri feuded with him throughout late-2001.
Tajiri won his first Cruiserweight Championship in October 22, 2001 on Raw. The title became the WWF Cruiserweight Championship when the WWF defeated The Alliance at Survivor Series 2001 on November 18 and replaced the WWF Light Heavyweight Championship. WWF was renamed World Wrestling Entertainment, and the roster was divided into two "brands": Raw and SmackDown!. Tajiri, along with Torrie Wilson, was drafted to SmackDown!, therefore making WWE Cruiserweight Championship a Smackdown exclusive title. Tajiri went on to lose the title to Billy Kidman on an episode on Smackdown! He would go on to beat Kidman at Backlash once again and won the WWE Cruiserweight Championship again only 19 days after losing it. He turned heel by forcing Wilson to dress like a geisha against her will and Tajiri would go on to lose the WWE Cruiserweight Championship to The Hurricane in a triple threat match between the two and Billy Kidman. Wilson eventually abandoned him during a WWE Crusierweight Championship match against The Hurricane, she did this by stripping on top of a table during the match that caused Tajiri to be counted out and later joined forces with Tajiri's rival, Maven. Later on, as a special guest referee, Tajiri would begin his second face run after being betrayed by a heel Jamie Noble after Noble caught Tajiri touching his girlfriend, Nidia. This led to several Cruiserweight Championship matches between the two including matches at No Mercy 2002 and Rebellion 2002. He also participated in his first Royal Rumble Match at Royal Rumble 2003.
Tajiri would leave the Cruiserweight division and moved to the tag team division where he formed various tag teams, many of which being some what comical, which included Rey Mysterio, Funaki and Rikishi.
Five days prior to Judgment Day, Chavo tore his biceps, forcing Eddie Guerrero to look for another partner. He chose Tajiri. 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 title by cheating. In addition, they also defeated Roddy Piper and his protégé Sean O'Haire in Madison Square Garden. After Guerrero and Tajiri lost the titles to Team Angle on the July 3 episode of SmackDown!, Guerrero turned on Tajiri, slamming him through the windshield of his low-rider truck. The next Smackdown! Guerrero said he did it because during the match Tajiri had accidentally hit his low-rider.
Tajiri would mark his return to the Cruiserweight division by taking on the champion Rey Mysterio and after losing he spat green mist in Mysterio's eye, turning him heel once again. On September 23, Tajiri would beat Rey Mysterio for the WWE Cruiserweight Championship which would be his third and last reign. Tajiri would successfully defend the championship in Mysterio's rematch at No Mercy 2003 after Akio and Sakoda, later known as "Kyo Dai", interfered in the match. Tajiri would however lose the championship after 93 days to Mysterio on SmackDown. Tajiri kept his heel persona going by spitting black mist in Nidia's eyes and "blinding" her (Nidia and Noble were both faces by this time.) Noble and Tajiri started a new feud, which quickly ended after Noble betrayed his blind girlfriend and turned heel again. Kyo Dai would quickly be separated from Tajiri and eventually split up after Tajiri refused the WWE writers proposal of Kyo Dai portraying Japanese gangsters, Tajiri feared that it might anger the real Japanese Yakuza if they saw the gimmick as an insult. At WrestleMania XX, Tajiri took part in a cruiserweight open for the WWE Cruiserweight Championship which was won by the reigning champion Chavo Guerrero, Jr..
In 2004 he had two chances to earn a WWE Title Shot. The first chance was in the 2004 Royal Rumble, where the winner would get a championship match at WrestleMania XX, but was eliminated by Rhyno. His second chance was in a battle royal on Smackdown!, in which the winner would face then-champion Brock Lesnar at the No Way Out pay-per-view. However, he lost once again after he was eliminated by the Big Show.
Following WrestleMania XX, Tajiri was drafted to Raw, where he turned face once again and feuded with the group of Eric Bischoff, Jonathan Coachman, and Lance Cade. He would later feud with the Evolution stable for a good portion of 2004. Also that year, he formed a tag team with Rhyno. This team dissolved quietly after a failed attempt at winning the Tag Team Championship from La Résistance at Unforgiven. On February 4, 2005, in Saitama Super Arena), Tajiri teamed with William Regal to defeat La Résistance for the World Tag Team Championship on an episode of Raw emanating from Japan. After several defenses against La Resistance (among others), their reign ended on May 1 at Backlash, when they were eliminated from a tag team turmoil match by La Résistance.
Tajiri lost a 3-Way Dance (that also featured Little Guido) to Super Crazy at ECW One Night Stand 2005 on June 12. Later that year, he formed a short-lived team with Eugene. In December 2005, Tajiri left WWE. His final televised WWE match was a loss to Gregory Helms on Heat. After the match, he received a standing ovation as a farewell.
Tajiri returned for a one-night appearance at WWE's ECW One Night Stand 2006 pay-per-view, teaming with Super Crazy to take on the Full Blooded Italians (F.B.I.) in a losing effort.
On February 12, 2008, Tajiri made an appearance at a WWE house show in Tokyo, where he accompanied William Regal to the ring for a match against Ric Flair, which Regal lost. Tajiri also appeared at the WWE WrestleMania Revenge Tours shows in England.
On June 13, 2016, Tajiri was announced as a participant in WWE's upcoming Cruiserweight Classic tournament. The tournament kicked off on June 23 with Tajiri defeating Damian Slater in his first round match. On July 14, Tajiri was eliminated from the tournament by Gran Metalik.
On December 3, at the NXT special at Osaka, Japan, Tajiri teamed with Akira Tozawa, in a losing effort to NXT Tag Team Champions DIY (Tommaso Ciampa and Johnny Gargano). On December 4, 2016, Tajiri announced he signed a full-time contract with WWE, and that he would make his return in early 2017. On the December 13 episode of 205 Live, vignettes for Tajiri's return began airing. On January 3rd 2017 Tajiri returned on 205 Live defeated Sean Maluta after the match Brian Kendrick tried to welcome Tajiri back but Tajiri spit green mist in Brian's face.