Ferguson served as vice president and director of hockey operations for the St. Louis Blues, and before that he was assistant general manager for the club for five seasons. In that role he evaluated players at the professional and amateur level and negotiated player contracts. Ferguson was also the president and general manager of the Worcester IceCats and was influential in the negotiation and acquisition of the Blues top minor league affiliate. He is a former chairman of the AHL's Competition Committee and also served on the league's Legal Affairs Committee.
On August 29, 2003, Ferguson became the 12th general manager of the Toronto Maple Leafs, being appointed at the age of 36. He succeeded Pat Quinn, who retained his duties as head coach after serving in a dual capacity for the previous four season. Leafs President Ken Dryden was shuffled to the post of Vice-Chairman and given a seat on MLSE's board of directors.
During the 2005-06 season, the first since the lockout, the Leafs narrowly missed the playoffs. The 2006 firing of Quinn upset some long time Leaf fans, with many calling for the firing of Ferguson himself. In 2007 Ferguson served as a member of Team Canada management at the 2007 IIHF World Championship in Russia. Serving as a member of team management, he collaborated with Steve Yzerman in selecting Canada's unbeaten gold medal roster, the youngest team to ever win a World Championship.
Entering the 2007-08 season the Leafs had posted a .577 points percentage during Ferguson's tenure, establishing franchise records for points (103), wins (45-tie), home wins (26) and road wins (23) in a season. The club reached at least 90 points and 40 wins in each of the three seasons played. However, the team failed to qualify for the playoffs in the last two of the four seasons under Ferguson. The team was out of a playoff position at the time of his dismissal, near the bottom of the league. Columnists frequently suggested that Ferguson was not prepared for the pressure of an avid hockey market such as Toronto.
After weeks of media speculation, on January 22, 2008, Ferguson was informed his Leafs' contract would not be renewed when it expires on June 30, 2008 and as a result was relieved immediately from his duties as general manager, and was replaced by former Maple Leafs GM Cliff Fletcher. Fletcher's attempt to rebuild the team was made further difficult as most of the key Leafs players, Mats Sundin, Tomas Kaberle, Bryan McCabe, Darcy Tucker and Pavel Kubina, all had no-trade clauses given by Ferguson that they refused to waive.
At the 2007-08 NHL Season's trade deadline, he provided analysis of the trades as they came in for TSN.