Gilmour began his NHL career with St. Louis in 1983.

When Doug joined the Cornwall Royals of the Ontario Hockey League, he was a solid defensive forward who could also score, although his size was considered a major stumbling block in the eyes of most NHL scouts. In 1980-81, his first year with the Royals, Gilmour was 5'9" and 150 pounds. Although he would gain a couple of inches in his three years in Cornwall, he didn't add many extra pounds. What did add up in the OHL were his offensive numbers. After an early injury curtailed his effectiveness in Cornwall's 1981 Memorial Cup championship, he returned to score 46 goals and 119 points in 1981-82.

Gilmour joined the Calgary Flames prior to the 1988-89 season.

Still, Gilmour's size worried management in St. Louis and he almost began his professional career in Germany when he couldn't reach a deal with the Blues. St. Louis finally signed him and he joined the team two weeks before the 1983-84 season. Gilmour found himself near the bottom of the team's depth chart at centre, but a depleted roster allowed him to play on the fourth line as a defensive specialist and he returned to his checking ways. The Blues' captain at the time, Brian Sutter, nicknamed Gilmour 'Killer' for his intensity.

Gilmour was part of the Flames' Stanley Cup winning team in 1989.

After another solid season in St. Louis, Gilmour was traded to the Calgary Flames at the beginning of the 1988-89 campaign. In Calgary, Gilmour continued his strong play in the playoffs, adding 22 points in 22 games as the Flames won the Stanley Cup in 1989. Gilmour scored the series-winning goal in Game Six of the Final against Montreal. Halfway through the 1991-92 season, Gilmour became increasingly disenchanted with his salary with the Flames and an arbitrator's decision that saw his salary increase less than he expected. He decided to leave the team, but only a few hours later he was traded to the Toronto Maple Leafs in a blockbuster deal involving 10 players; the largest trade in league history.

Gilmour was sent to the Toronto Maple Leafs mid-way through the 1991-92 season.

Gilmour had 111 points the next season, earning his second consecutive spot in the All-Star Game. He once again led the Leafs to the semi-finals in the playoffs. Gilmour was named the team captain in 1994-95 before the lockout-shortened season and remained a popular player in Toronto even as the team began to struggle. When the Leafs went into rebuilding mode midway through the 1996-97 season, Gilmour was sent to the New Jersey Devils. He spent one full season with the defence-oriented Devils and was signed as a free agent by the Chicago Blackhawks in the summer of 1998.

Gilmour holds the Leafs record for points in a season with 127.

In his first game back with the Leafs, Gilmour injured his knee in an innocent collision which ended his season. He officially announced his retirement on September 8, 2003 after Toronto Maple Leaf General Manager John Ferguson Jr. declined to re-sign him. Over the course of his distinguished playing career, Gilmour registered 1414 points on the strength of 450 goals and 964 assists in 1,474 regular season games. He added 188 points (60 goals and 128 assists) in 182 playoff games.

On January 31, 2009, Gilmour became the seventeenth player to be honoured by the Toronto Maple Leafs when his number 93 was raised to the rafters of the Air Canada Centre. In 2011, Doug Gilmour was selected for Induction to the Hockey Hall of Fame.