MacKinnon, who has 15 points (eight goals, seven assists) during an eight-game point streak, leads the NHL with 61 points (30 goals, 31 assists) in 35 games.
Cale Makar and Brock Nelson each had a goal and two assists, Martin Necas also scored, and Valeri Nichushkin and Gabriel Landeskog each had two assists for the Avalanche (26-2-7), who have won five in a row and extended their point streak to eight games (7-0-1). Mackenzie Blackwood made 28 saves.
Ryan Hartman scored, and Jesper Wallstedt made 37 saves for the Wild (22-10-5), who also had their home point streak end at 14 games (12-0-2).
Necas gave the Avalanche a 1-0 lead at 18:28 of the first period, roofing a one-timer over Wallstedt’s glove from the right hash marks.
Sam Malinski appeared to make it 2-0 on a rebound in front at 4:12 of the second period, but Minnesota challenged the play for offside, and the call was reversed after a video review.
MacKinnon, however, did extend the lead to 2-0 with a power-play goal at 13:37, scoring with a one-timer from the edge of the left circle.
Makar made it 3-0 at 18:33 with another power-play goal after Marcus Foligno was assessed two minor penalties (interference and cross-checking) at 15:07. He scored glove side through a screen following a face-off win by Landeskog.
Hartman cut the deficit to 3-1 at 5:15 of the third period, scoring in front after Jonas Brodin’s point shot hit off the right post.
Nelson made it 4-1 at 15:52 with a one-timer from the right circle, and MacKinnon scored into an empty net at 17:35 for the 5-1 final.