MacKinnon has 21 points (six goals, 15 assists) during his point streak, which is the longest active in the NHL. He also extended his season-opening home point streak to 15 games (nine goals, 19 assists).
Valeri Nichushkin scored twice, Mikko Rantanen had a goal and two assists, and Sam Malinski scored his first NHL goal and had an assist for the Avalanche (18-9-2), who have won two straight. Ivan Prosvetov made 29 saves.
Zach Benson scored, and Ukko-Pekka Luukkonen made 25 saves for the Sabres (12-15-3), who had a three-game point streak end (2-0-1).
Rantanen gave the Avalanche a 1-0 lead at 5:25 of the first period after he took a drop pass from MacKinnon and scored on a wraparound.
Nichushkin made it 2-0 at 10:28, scoring past a lunging Luukkonen after Fredrik Olofsson's wraparound at the left post popped out to him through the legs of JJ Peterka.
Miles Wood extended the lead to 3-0 at 11:55, electing to shoot on a 2-on-1 with Logan O’Connor and scoring blocker side from the right circle.
Benson cut it to 3-1 at 18:38. He finished a rebound in front after Rasmus Dahlin's initial shot deflected to him off the shin of Josh Manson.
Buffalo had been outshot by Colorado 15-0 prior to Dahlin's attempt.
Malinski, who was playing in his seventh NHL game, pushed it to 4-1 at 2:40 of the third period with a one-timer from the top of the left circle that went over the glove of Luukkonen.
Nichushkin made it 5-1 at 13:11 when he tapped in a backdoor pass from MacKinnon on a power play.
