Kubalik scored a power-play goal for the Blackhawks at 16:47 of the first to make it 3-1.
Nazem Kadri gave Colorado a 4-1 lead on a rebound at 16:12 of the second period.
Murphy scored at 15:31 of the third for the 4-2 final.
Avalanche assistant coach Ray Bennett filled in for coach Jared Bednar, who is also in NHL COVID-19 protocol.
"Really good start by us, obviously," Bennett said. "I thought the first 10 or 12 minutes of the game were almost a script in terms of our effort and energy and execution, and real good emotional engagement."
Kuemper made two key saves against Blackhawks center Kirby Dach during the second period to preserve a 3-1 lead. The first came on a breakaway at 12:01 after Dach stole the puck from Samuel Girard at the blue line. Kuemper denied Dach again at 15:45 on a 2-on-1, and Kadri scored on the ensuing rush the other way.
"You just try to stay patient," Kuemper said. "Obviously he's a really skilled young player with a good shot. I just tried to stay patient and read his release.
"It was a lot of fun to finally play a real game with this group. You know, (there's) a lot of talent in this locker room, so it's fun to be a part of and it's always fun to start off with a big win with the season and just got to keep building out."
NOTES: Blackhawks center Jonathan Toews, who missed all of last season because of chronic immune response syndrome, had two shots on goal in 17:15 of ice time. … Avalanche general manager Joe Sakic said MacKinnon could return against the St. Louis Blues on Saturday. MacKinnon finished eighth in the NHL with 65 points (20 goals, 45 assists) and was plus-22 in 48 games last season. He finished third in voting for the Hart Trophy as NHL MVP. "He's asymptomatic and feeling good ... but hopefully he'll be able to test out," Sakic said.