MacKinnon has scored in four straight games and leads the NHL with 22 goals and 46 points.
Brock Nelson scored, and Gabriel Landeskog had two assists for the Avalanche (19-1-6), who are 14-0-3 during the point streak, the second-longest in franchise history (19 games in 2021-22).
Scott Wedgewood allowed one goal on 11 shots before leaving the game at 12:28 of the second period with an upper-body injury. Mackenzie Blackwood made 11 saves in relief.
Linus Karlsson scored, and Kevin Lankinen made 28 saves for the Canucks (10-14-3), who have lost three straight and are 1-5-1 in their past seven games.
Karlsson made it 1-0 Vancouver at 2:55 of the first period when he beat Parker Kelly in a foot race, caught a pass from Arshdeep Bains atop the crease, and went forehand-backhand and around the right leg of Wedgewood.
MacKinnon tied it 1-1 at 19:23 of the first when the rebound of Sam Malinksi’s point shot from the right wall, which was tipped by Devon Toews, went off the right pad of Lankinen and to MacKinnon at the left circle for the shot past the paddle.
Nelson scored to give Colorado a 2-1 lead when he beat Max Sasson into the zone from the blue line and finished a pass from Landeskog over the blocker at 13:52 of the second period.
MacKinnon extended the lead to 3-1 with a one-timer from the right circle that went short side over the glove at 19:26. Landeskog skated around the bottom of the circle and fed him back across for the shot.
Vancouver forward Evander Kane left the game at 16:30 of the third period with an injury.
