Cale Makar had a goal and an assist, and Martin Necas had two assists for the Avalanche (3-0-1). Scott Wedgewood made 28 saves.
Tage Thompson scored his first goal of the season, and Alex Lyon made 34 saves for the Sabres (0-3-0).
MacKinnon gave Colorado a 1-0 lead at 3:14 of the first period, taking a pass from Necas in the right circle, cutting to the left circle and putting a backhand over Lyon’s right pad.
Thompson tied it 1-1 with a wrist shot from high in the zone that beat Wedgewood blocker side at 16:32.
Makar put the Avalanche ahead 2-1 at 4:32 of the second period with his first of the season. Valeri Nichushkin intercepted Rasmus Dahlin‘s clearing attempt inside the zone and took it to the net before sending it over to Makar for the tap-in.
With the teams skating 4-on-4, MacKinnon used Owen Power as a screen in the left circle and put a wrist shot under Lyon’s right arm to make it 3-1 at 11:59 of the second.
Necas appeared to give Colorado a 4-1 lead at 7:26 of the third period, but Buffalo used a coach’s challenge for offside, and the call on the ice was overturned.
