Matt Duchene and Brandon Yip gave the home team a winning advantage early in the second period and the Avalanche held off a furious onslaught after Cody Franson had halved the deficit to seize sole possession of the Northwest Division lead.
"It's great," Duchene told reporters. "It's right where we want to be, especially with Vancouver playing well and creeping up on us. This was our game in hand, and it's huge to win it."
Craig Anderson made 29 saves, including 13 in the third period, as Colorado (29-15-6) registered a first win of the season against the Predators.
The victory continues a considerable turnaround for Colorado, who finished last in the Western Conference a year ago but are third following this victory.
The Predators (29-19-3) pushed them close and thought they had leveled the scores at 2-2 with 7:31 remaining only for the score to be canceled out as Patric Hornqvist was penalized for goalie interference.
"I may have touched him a little bit, but I wasn't sure if he was outside the blue (crease) or not," Hornqvist said.
"The ref made the call, and that's life sometimes. I didn't run into him, maybe backed into him. It's a hard situation."
All three of the game's goals were scored on power-plays, with Duchene's opening goal coming on a five-on-three advantage at 13:46 in the first.
It was a third goal in three games for Duchene, who is the NHL's leading rookie points scorer with 34.
The Predators have now lost three straight and sit a distant second behind the Chicago Blackhawks in the Central Division.
(Writing by Jahmal Corner in Los Angeles; Edited by Patrick Johnston)