Colorado, which hasn't lost in regulation since a 5-2 defeat against the Winnipeg Jets on Nov. 9, has won six straight on the road and is 9-0-2 during its point streak.
"We came out really sluggish in the first period; we looked like the team that played and traveled last night, but [Varlamov] kept us in the game," Avalanche coach Jared Bednar said. "We really flipped the script going into the second period and I liked the way we played from there."
Jonathan Bernier made 27 saves for Detroit (12-12-3), which won 4-2 at the Boston Bruins on Saturday. The Red Wings were outshot 22-11 over the final two periods.
"I don't think playing yesterday had anything to do with that," Red Wings defenseman Niklas Kronwall said. "We just had too many turnovers that left us with too much time in our own zone for no reason."
The Red Wings were missing three of their top scorers in one stretch of the third period; Tyler Bertuzzi and Anthony Mantha were in the penalty box after fighting majors, and Dylan Larkin was in concussion protocol following a hit from Avalanche defenseman Patrik Nemeth.
"We were a little shorthanded there because we only dressed 11 forwards and lost three of them," Red Wings coach Jeff Blashill said. "But the concussion protocol is there to protect the safety of the players, so you can't complain about them checking on [Larkin]."
The Avalanche took a 1-0 lead at 4:54 of the second period, six seconds after Jonathan Ericsson was called for holding. Landeskog passed to Mikko Rantanen at the side of the net, where he found MacKinnon in the slot for his 19th goal.