Sven Andrighetto scored two goals, Tyson Barrie had a goal and two assists, and Mikko Rantanen had a goal and an assist for Colorado.
Semyon Varlamov made 30 saves before leaving with 6:25 left in the third period with a lower-body injury after Blackhawks forward Tomas Jurco slid into him in the crease. Jonathan Bernier replaced him and made three saves.
Collin Delia made 31 saves for the Blackhawks (32-37-10), who are 2-1-1 in their past four games and have been eliminated from playoff contention.
"They're good, very skilled," Delia said. "Move the puck very well, a very fast pace. It's good for me to get in there and see that, see a dominant team like them, how they move the puck, to get my timing down. It's good."
Andrighetto scored a power-play goal to give the Avalanche a 1-0 lead at 18:54 of the first period. After receiving a pass from Samuel Girard, Andrighetto split two Blackhawks defensemen before beating Delia glove side.
"I just tried to get as much speed as I could on the power play breakout," said Andrighetto, who missed the past three games with a lower-body injury. "With a man advantage, we have more room. I saw the room and I took it."