He was chosen 12th overall by the Colorado Avalanche in the 1998 NHL Entry Draft. After his final season in Halifax, Tanguay joined the AHL's Hershey Bears before making his NHL debut in 1999-00, scoring 17 goals as an NHL rookie. The next year Tanguay broke through with 27 goals and registered 21 post-season points while helping the Avalanche capture their second the Stanley Cup in franchise history. Tanguay scored two key goals in the seventh game of the finals versus the New Jersey Devils and was a key to the fortunes of the club after the injuries felled star pivot Peter Forsberg.

A versatile forward, Tanguay's offensive numbers dropped in 2001-02 before rebounding the following year with 67 points. In 2003-04, Tanguay established a career high in assists (54) tying teammate Joe Sakic for second in the league and points (79) despite missing 13 games in the latter stages of the season.

On June 24, 2006 Alex Tanguay and a 2007 or 2008 conditional draft pick were sent to Calgary for Jordan Leopold and a 2006 second-round draft pick. In his first season as a Flame, Tanguay was a point-per-game player and he appeared in his 500th NHL Game. However, his point product slipped the following season and the Flames dealt the Quebec native at the 2008 NHL Draft to the Montreal Canadiens for the club's 1st round choice (Greg Nemisz) in 2008 Entry Draft and their 2nd round choice in 2009 Entry Draft.

In the summer of 2009, Tanguay was again on the move. This time he was an unrestricted free agent and signed with the Tampa Bay Lightning. Ironically, it was in a game against the Lightning the previous season that Tanguay suffered a shoulder injury that would end his season.

On July 1, 2010, Tanguay surprised the hockey world when as an unrestricted free agent he chose to sign with his former club, the Calgary Flames.