It was Colorado's first game since sweeping the Columbus Blue Jackets at the 2022 NHL Global Series in Finland on Nov. 4-5, and first home game since Oct. 21.
Logan O'Connor scored twice, and Alexandar Georgiev made 32 saves for the Avalanche (7-4-1), who have won three straight.
"I thought we had a great second period, but first period gave up too much, kicked the puck around a lot. A lot of icings. Just not sharp," Colorado coach Jared Bednar said. "We did some good things on the offensive side of it.
"I thought we had some guys that played outstanding tonight.
[Nathan] MacKinnon
was phenomenal. Logan O'Connor, phenomenal. Mikko had a pretty good night finishing. We capitalized on our chances in this game, they didn't. That was the difference."
Eeli Tolvanen, Ryan Johansen, and Roman Josi scored, and Kevin Lankinen made 30 saves for the Predators (5-8-1), who went 2-3-0 on their five-game road trip.
"You can't be a hard team to play against when you give up easy offense like we have multiple times on this road trip, and then particularly tonight," Nashville coach John Hynes said. "We've got to be smarter. I think you look at some of the chances we give up, it's unacceptable. The awareness, whether it's some decisions with the puck or it's decisions without the puck, we give up two breakaway goals in the second period. We've got to be smarter than that."