Benoit simultaneously entered into a long-running feud with Jericho for the Intercontinental title, with the two meeting at Backlash, Judgment Day and SummerSlam; Benoit winning all three matches. The feud finally culminated in Jericho defeating Benoit in a ladder match at the Royal Rumble in January 2001. Benoit won the Intercontinental title three times between April 2000 and January 2001.
In early 2001, Benoit broke away from The Radicalz (who had recently reformed three months earlier) and turned babyface, feuding first with his former stablemates and then with Kurt Angle, whom he wrestled at WrestleMania X-Seven. The feud continued after Benoit stole Angle's cherished Olympic Gold Medal. This culminated in a match at Judgment Day where Angle won a two out of three falls match with the help of Edge and Christian. In response, Benoit teamed up with his former rival Jericho to defeat Edge and Christian in that night's Tag Team Turmoil match.
The next night on Raw in San Jose, California, Jericho and Benoit challenged WWF Tag Team Champions Stone Cold Steve Austin and Triple H for their title. On May 21, 2001, Jericho and Benoit ended their reign and as a result of the win, Benoit aided Jericho in becoming the fourth Grand Slam Champion when he captured the WWE title later in December.
The pair used the win as a springboard to challenge Austin for his world title. Benoit got two title matches the following week, first losing in a manner similar to the Montreal Screwjob in Calgary and then just barely losing to Austin in Benoit's hometown of Edmonton. Unfortunately, Benoit suffered a neck injury in a four-way TLC match that required surgery with Dr. Lloyd Youngblood. Despite this, he continued to wrestle until the King of the Ring, where he was pinned in a triple threat match versus Austin and Jericho. Benoit missed the next year due to his neck injury, missing the entire Invasion storyline.
During the first WWE Draft, he was the third superstar picked by Vince McMahon to be part of the new SmackDown! roster, although still on the injured list. However, when he returned, he did so as a member of the Raw roster. On his first night back, he turned heel again and aligned himself with Eddie Guerrero, and he feuded with Steve Austin briefly. He and Guerrero were then moved to SmackDown during a storyline "open season" on wrestler contracts, with Benoit taking his newly won Intercontinental championship with him. Rob Van Dam defeated Benoit at SummerSlam and returned the title to Raw.
After returning to SmackDown! on October 20, 2002, he was crowned the first winner of the WWE Tag Team Championship, alongside foe and partner Kurt Angle. In this, Benoit consecutively helped to crown the fifth Grand Slam Champion, as the tag title was the only remaining title Kurt needed. They became tweeners after betraying Los Guerreros.
Angle won his third WWE Championship from The Big Show at Armageddon, and Benoit faced him for the title at the 2003 Royal Rumble. Although Benoit lost the match, he received a standing ovation for his efforts. Benoit returned to the tag team ranks, teaming with the returning Rhyno. At WrestleMania XIX, the WWE Tag Team Champions, Team Angle (Charlie Haas and Shelton Benjamin), put their belts on the line against Benoit and his partner Rhyno and Los Guerreros in a triple threat tag team match. Team Angle retained when Benjamin pinned Chavo.
Benoit then feuded with John Cena and the Full Blooded Italians, teaming with Rhyno occasionally. In June 2003, the United States Championship was reactivated and Benoit participated in the tournament for the belt. He lost in the final match to Eddie Guerrero at Vengeance. The two feuded over the title for the next month, and Benoit went on to defeat the likes of A-Train, Big Show, and Brock Lesnar by submission. General Manager Paul Heyman had a vendetta against Benoit along with Lesnar, preventing him from gaining a shot at Lesnar's WWE Title.
When Benoit won a qualifying match for the 2004 Royal Rumble against the Full Blooded Italians in a handicap match with John Cena, Heyman named him as the number one entry, but Benoit swore victory. On January 25, 2004 Benoit won the Royal Rumble by last eliminating Big Show, and thus earned a world title shot at WrestleMania XX. As a result of the long-standing Royal Rumble tradition that the winner receives a shot at the world champion at WrestleMania, and with Benoit being on the SmackDown! brand at the time it was assumed that he was going to compete for the WWE Championship. Benoit, however, exploited a "loophole" in the rules and appeared on Raw the following night to challenge World Heavyweight Champion Triple H. This "loophole" clause has become standard storyline practice, with the Royal Rumble winner being free to choose the title for which he will challenge. Though the match was originally intended to be a one-on-one match, Shawn Michaels, whose Last Man Standing match against Triple H at the Royal Rumble for the World Heavyweight Championship ended in a draw, thought that he deserved to be in the main event. When it was time for Benoit to sign the contract putting himself in the main event, Michaels superkicked him and signed his name on the contract, which eventually resulted in a Triple Threat match between Michaels, Benoit, and the champion, Triple H.
On March 14, 2004, at WrestleMania XX, Benoit won the World Heavyweight Championship by forcing Triple H to tap out to his signature submission move, the Crippler Crossface., marking the first time the main event of a WrestleMania ended in submission. After the match, an emotional Benoit celebrated his win with the then-reigning WWE Champion Eddie Guerrero. The rematch was held at Backlash in Benoit's hometown of Edmonton. It was Michaels who ended up submitting to Benoit's Sharpshooter, allowing Benoit to retain his title. The next night in Calgary, he and Edge won the World Tag Team title from Batista and Ric Flair, making Benoit a double champion.
The three months following his victory at Backlash, Benoit and Edge engaged in a rivalry with La Résistance for the World Tag Team Championship, which saw a series of matches, while simultaneously having confrontations with Kane over the World title. Benoit wrestled in two matches at Bad Blood in his respective rivalries; he and Edge failed to regain their World Tag Team title while he successfully defended the World title against Kane. A month later at Vengeance, Benoit retained the title against Triple H.
On August 15, 2004, Benoit was defeated by Randy Orton for the World Heavyweight Championship at SummerSlam. Benoit then feuded with Edge (who had turned into a crazed heel with severe anger management problems), leading to Taboo Tuesday where Benoit, Edge, and Shawn Michaels were all put into a poll to see who would face Triple H for the World Heavyweight title that night. Michaels received the most votes and as a result, Edge and Benoit were forced to team up to face the then tag team champions, La Résistance, in the same night. However, Edge deserted Benoit during the match and Benoit was forced to take on both members of La Résistance by himself. He still managed to win the World Tag Team title. At Survivor Series, Benoit sided with Randy Orton's team while Edge teamed with Triple H's team, and while Edge was able to pin Benoit after a Pedigree, Orton's team won.
The Benoit-Edge feud ended at New Year's Revolution. The feud stopped abruptly, as Edge feuded with Shawn Michaels, and Benoit entered the Royal Rumble. The two then continued to have matches in the following weeks until the two of them, Chris Jericho, Shelton Benjamin, Kane, and Christian were placed in the Money in the Bank ladder match at WrestleMania 21. Edge won the match by knocking Benoit off of and smashing his arm with the ladder. The feud finally culminated in a Last Man Standing match at Backlash, which Edge won with a brick shot to the back of Benoit's head.
On June 9, Benoit returned to SmackDown! after being the first man selected by the SmackDown! brand in the 2005 Draft Lottery and participated in an ECW-style revolution against the SmackDown! heels. Benoit appeared at One Night Stand, defeating Eddie Guerrero. At the end of the night he delivered a flying headbutt to former Raw General Manager Eric Bischoff.
On July 24 at The Great American Bash, Benoit failed to win the WWE United States Championship from Orlando Jordan, but he faced him in a rematch at SummerSlam. Benoit defeated Jordan in 25 seconds with the Crippler Crossface to win the title. On the next two editions of SmackDown!, Benoit defeated Jordan by submission in 23.4 seconds and 22.5 seconds, respectively. Two weeks later, Benoit defeated Jordan by submission in 49.8 seconds. Benoit then started wrestling Booker T in some friendly competitions, but it was all a ploy, as Booker and his wife, Sharmell, cheated Benoit out of the US title on an episode of SmackDown!.
On November 13, 2005, Eddie Guerrero was found dead in his hotel room. The following night, Raw held a Guerrero tribute show hosted by both Raw and SmackDown! superstars. Benoit was devastated at the loss of his best friend and was very emotional during a series of video testimonials, eventually breaking down on camera. The same week on SmackDown! (taped on the same night as Raw), Benoit defeated Triple H in a tribute match to his fallen friend. Following the contest, Benoit, Helmsley, and Dean Malenko all assembled in the ring and pointed to the sky in salute of Guerrero.
After controversy surrounding a US title defense against Booker T, Theodore Long set up a "Best of Seven" series between the two. Booker T won three times in a row, due largely to his wife's interference, and Benoit faced elimination in the series. Benoit won the fourth match to stay alive, but after the match, Booker suffered a legitimate groin injury, and Randy Orton was chosen as a stand-in. Benoit defeated Orton twice by disqualification. However, in the 7th and final match, Orton defeated Benoit with the help of Booker T, Sharmell, and Orlando Jordan, and Booker captured the US title. Benoit feuded with Orton for a short time, only to compete against Booker for the US title. Benoit was given one last chance at the US title at No Way Out and won it by making Booker submit to the Crippler Crossface, ending the feud. Soon after, Benoit defeated Orton in a No Holds Barred match on SmackDown! via Crippler Crossface.
The next week on SmackDown!, Benoit kayfabe broke John Bradshaw Layfield's (JBL) hand (JBL actually needed surgery to remove a cyst). A match was set up for the two at WrestleMania 22 for Benoit's title, and for the next several weeks, they attacked each other. At WrestleMania, JBL won the match with an illegal cradle to win the title. Benoit used his rematch clause two weeks later in a steel cage match on SmackDown!, but JBL again won with illegal tactics. Benoit then entered the King of the Ring tournament, only to be defeated by Finlay in the opening round, after Finlay struck Benoit's neck with a chair and delivered a Celtic Cross. At Judgment Day, Benoit gained some revenge by defeating Finlay with the Crippler Crossface in a grudge match. On the following edition of SmackDown!, Mark Henry brutalized Benoit during their match, giving him (kayfabe) back and rib injuries and causing him to bleed from his mouth. Benoit then took a sabbatical to heal nagging shoulder injuries.
On October 8, Benoit made his return at No Mercy, defeating William Regal in a surprise match. Later that week, he won his third United States Championship from Mr. Kennedy. Benoit then engaged in a feud with Chavo and Vickie Guerrero. He wanted answers from the Guerreros for their rash behavior towards Rey Mysterio, but was avoided by the two and was eventually assaulted. This would lead to the two embarking on a feud with title implications at the coming two pay per views. The feud would culminate with one last title match as a No disqualification match, which was also won by Benoit. Afterward, Montel Vontavious Porter (MVP), who claimed that he was the best man to hold the US title, challenged Benoit for the title at WrestleMania 23, where Benoit retained. Their rivalry continued with similar results again at Backlash. At Judgment Day, however, MVP gained the upper hand and won the title in a two out of three falls match.
On the June 11 edition of Raw, Benoit was drafted from SmackDown! to ECW as part of the 2007 WWE Draft, after losing a match to Bobby Lashley. Benoit won his ECW debut match teaming up with CM Punk and defeating Elijah Burke and Marcus Cor Von by disqualification. On June 19, Benoit wrestled his last match, defeating Burke in a match to determine who would compete for the vacated ECW World Championship at Vengeance. Benoit missed the weekend house shows, telling WWE officials that his wife and son were vomiting blood due to food poisoning. When he failed to show up for the pay-per-view, viewers were informed that he was unable to compete due to a "family emergency" and he was replaced in the title match by Johnny Nitro. Nitro won the match and became ECW World Champion.
Benoit died on June 24, 2007 after strangling his wife, Nancy, suffocating his son, and finally hanging himself.
WWE canceled the scheduled three-hour long live Raw show on June 25, and replaced the broadcast version with a tribute to his life and career.