MacKinnon also had an assist, Cale Makar had a goal and two assists, Artturi Lehkonen had a goal and an assist, and Jonathan Drouin had three assists for the Avalanche (49-26-6), who had lost two straight. Alexandar Georgiev made 20 saves.
Colorado remained five points behind the Dallas Stars for first in the Central Division.
Matt Boldy had a goal and an assist, Kirill Kaprizov scored, and Filip Gustavsson made 27 saves for the Wild (37-32-9), who were eliminated from Stanley Cup Playoff contention.
Lehkonen made it 1-0 Colorado with a power-play goal at 4:33 of the first period. He one-timed MacKinnon’s centering pass from just below the left hash marks.
MacKinnon scored his first of the game to extend the Avalanche lead to 2-0 when he skated through Wild defensemen Zach Bogosian and Jonas Brodin before putting a wrist shot short side past the glove at 8:38.
Kaprizov scored to make it 2-1 with a power-play goal at 10:14, hammering home his own rebound after Georgiev sticked his initial attempt at a wraparound out of the crease.
Boldy tied it 2-2 with a power-play goal when he tipped in the centering pass from Mats Zuccarello at the top of the crease at 19:40 of the first.
Makar made it 3-2 when he walked across the blue line from right to left before turning and firing a wrist shot that went far side at 6:15 of the second period.
MacKinnon scored again to make it 4-2 when he sped around Wild defenseman Brock Faber in the neutral zone and skated in alone before firing a wrist shot from the right dot past the blocker at 14:50 of the second period. MacKinnon became the sixth player in Avalanche/Quebec Nordiques history to reach 50 goals in a season.
He completed the hat trick to make it 5-2 at 19:08, again using his speed to split the defensemen in the neutral zone before deking Gustavsson and sending his shot past the glove.
