Sittler grew up in St. Jacobs, Ontario and played minor hockey in nearby Elmira. He was drafted out of the Junior C Elmira Sugar Kings by the London Nationals, soon renamed the London Knights, and played under coaches Turk Broda and Bep Guidolin. Sittler was selected eighth overall by the Maple Leafs in the 1970 NHL Amateur Draft. He was named team captain on September 10, 1975 after Dave Keon left the team to play in the World Hockey Association following a contract dispute with Leafs owner Harold Ballard.

On February 7, 1976 in a game between Toronto and Boston at Maple Leaf Gardens, Sittler set an NHL record that still stands by tallying 6 goals and adding 4 assists for 10 points. All his points were scored against rookie goalie Dave Reece in an 11-4 Maple Leaf victory.

Sittler’s relationship with Ballard slowly deteriorated, particularly after Ballard hired Punch Imlach as general manager in July 1979. Imlach and Ballard both had strained relations with NHLPA executive director Alan Eagleson who, as a player agent, represented more than a dozen Leafs, including Sittler and his best friend and linemate, Lanny McDonald. Imlach believed Sittler had too much influence on the team and tried to undermine his authority with the players. When Sittler and goaltender Mike Palmateer agreed to appear on the TV show Showdown, as negotiated by the NHLPA, Imlach went to court to try to get injunction to stop them. When Imlach said he was open to offers for Sittler from other teams, Eagleson said it would cost $500,000 to get Sittler to waive the no-trade clause in his contract. So, instead of trading Sittler, Imlach sent McDonald to the woeful Colorado Rockies on December 29, 1979. In response, Sittler ripped the captain’s C off his sweater, later commenting a captain had to be the go-between with players and management, and he no longer had any communication with management. Ballard would liken Sittler’s actions to burning the Canadian flag.

In July 1980 Sittler presented Terry Fox with his NHL All-Star Game jersey in Nathan Phillips Square in front of a crowd of over 10,000 supporters. Fox had said Sittler was one of his favourite athletes.

During the 1981–82 season, Ballard considered Imlach’s health to be too poor for him to continue as general manager. But even with Imlach gone, Sittler’s relationship with the Leafs worsened to the point where he told Ballard and acting general manager Gerry McNamara at the end of November he would waive his no-trade clause if he was sent to the Flyers or the Minnesota North Stars. In the first week of December, Eagleson agreed to terms with Flyers’ owner Ed Snider and North Stars’ general manager Lou Nanne. But it took another seven weeks for the Leafs to make a deal. During that time, Sittler added the Islanders and Buffalo Sabres to the list of teams he could be traded to. On January 5, 1982, on advice from his physician, Sittler walked out on the Leafs, saying he was “mentally depressed” because a trade was taking so long to complete.

Finally, on January 20, 1982, the 31-year-old Sittler was traded to the Flyers for Rich Costello plus the Hartford Whalers’ second-round pick in the 1982 draft (used by the Leafs to select Peter Ihnačák), and future considerations, which ended up being Ken Strong. Only Ihnacak would play regularly for the Leafs. In 1980, Imlach had rejected an offer from Philadelphia, who were said to be willing to trade Rick MacLeish and André Dupont for Sittler.

Sittler was elected to the Hockey Hall of Fame in 1989. In 1991, a year after Ballard died, he rejoined the Maple Leafs organization as a consultant under general manager Cliff Fletcher, and also performs public relations duties for the team on an ongoing basis. In 1998, he was ranked number 93 on The Hockey News’ list of the 100 Greatest Hockey Players. On February 8, 2003, the Leafs honoured Sittler by adding a banner with his number 27 to those already hanging in the Air Canada Centre for other Leafs greats. In a ceremony, Sittler, with his three grown children at his side, paid tribute to his wife Wendy, who had died of cancer one year previous.

With the Flyers in 1982–83, Sittler earned his fourth All-Star game appearance and he returned to the Flyers the following season. Before the 1984–85 season, Sittler was told he would be named the Flyers’ team captain. On the day the announcement was to be made—Sittler even had a brief speech prepared—he was instead told by Flyers’ newly appointed general manager Bobby Clarke he had been traded to the Detroit Red Wings for Murray Craven and Joe Paterson. It was this incident that Sittler described as the biggest disappointment of his life. “Clarke can’t come close to realizing how much he hurt me, and my family, that day,” he wrote in his 1991 autobiography. Sittler contemplated retirement and did not report to the Wings for a few days, but then joined the team. He had an unproductive season, struggling to get ice time under coach Nick Polano, and finishing the year with the worst goals-per-game average of his NHL career. The Red Wings bought out Sittler’s contract after the end of the season. He received a one-year contract offer from the Vancouver Canucks, but decided to retire.

In 2004, Sittler appeared as himself in a brief cameo in season two, episode two of the Canadian sitcom, Corner Gas. The episode centred around the disputed ownership of one of Sittler’s rookie cards.

Sittler was inducted into Canada’s Walk of Fame on August 23, 2016. On October 15, 2016 number 27 worn by Sittler and Frank Mahovlich was officially retired by the Toronto Maple Leafs, along with the numbers of 16 other players, to celebrate the team’s 100th season.