Brandon Reid, Jason Jaffray, and Shaun Heshka scored for Manitoba (20-13-5-4), while Jannik Hansen added two assists. Duncan Milroy and Michael Lambert replied for Hamilton (22-16-1-1).
Manitoba's fourth win in a row lifted the Moose into a tie for first place with Rochester in the North Division with 49 points apiece. The Americans, however, have six games in hand.
The Moose have earned at least one point in 14 of their last 15 games.
The Bulldogs, who have lost six of their last seven, remain in third, three points back of the division leaders.
Reid opened the scoring with a power-play goal just 1:34 into the game after Hamilton defenceman Mathieu Biron was sent off for cross-checking. The diminutive centre snapped a wrist shot from directly in front and beat Hamilton goaltender Jaroslav Halak with a high drive.
The Moose increased their lead to 2-0 about 10 minutes later when Jaffray scored short-handed. Defenceman Prestin Ryan raced down the left side and fed a perfect pass to Jaffray, who beat an out-of-position Halak for his 23rd goal of the season.
Smith's ninth goal of the season at 5:48 of the second period increased the Moose lead to 3-0. Hansen swept out from behind the net and slid the pick to the front of the crease, and Smith backhanded the puck along the ice and caught the far corner of the net.
Lambert ended Drew McIntyre's shutout bid at 3:16 of the third when he raced across the blue-line and unleashed a hard slapshot with the puck sailing over MxIntyre's shoulder and just under the crossbar.
Heshka restored the three-goal Moose advantage at 12:12 of the third period when his slapshot from just inside the blue-line beat Halak to the far corner.
Duncan Milroy got one back for Hamilton less than two minutes later with a power-play goal.
McIntyre made 23 saves for the Moose, while Halak stopped 21 shots for the Bulldogs.
The two teams have now split six games this season and meet again Friday night.