The centre scored two goals in regulation and added another in a shootout along with teammate P.A. Parenteau, as the Avs stopped a two-game losing skid with a 4-3 victory over the Winnipeg Jets.
The Jets went on the power play three times in the first seven minutes of the game, coming away with one even-strength and one power-play goal against goalie Semyon Varlamov to go up 2-0.
Duchene finally stopped the bleeding with his team-leading 13th goal of the season at 15:08 of the first when he went in alone on Ondrej Pavelec and got a high shot past the netminder.
"We got behind the eight ball in penalties," said Duchene, who hadn't scored in seven games after returning from a stomach injury.
"They started really well. You've got to tip your hat sometimes. Getting that one, kind of gave us some life and got the momentum going again so it was a big goal."
Duchene, who also had an assist, scored his second goal to give the Avalanche a 3-2 lead with 1.6 seconds left in the second period when he backhanded a rebound into the open side of the net as Pavelec tried to slide back.
Ryan O'Reilly had tied the game 2-2 at 14:27 and added an assist for the Avs (21-9-0).
Varlamov faced 38 shots, including five in overtime. Pavelec made 20 saves in regulation and three in overtime.
Winnipeg used its fifth power play to tie the game 3-3 at 10:00 of the third period after Mark Scheifele sent a shot from the point that Wheeler put in past a screened Varlamov with two seconds left in a tripping penalty to Cory Sarich.
Duchene's shootout goal beat Pavelec after he lifted one leg and paused for a split second before firing the puck. Parenteau followed with a high shot over Pavelec's glove.
Colorado coach Patrick Roy was proud of his team for rebounding after being down 2-0.
"That's the dangerous part of this because sometimes when you get behind you have the tendency to go individually and that's not what we did tonight," Roy said.
"We sticked to the plan, we sticked together, we played as a team … 2-1 by a super play by Dutchy, Matt Duchene, and then after (Nathan) MacKinnon did another really good play.
"An outstanding defensive play by Duchene, but a great play by MacKinnon, put the puck on the net and picked up the rebound by Matt."
Jets coach Claude Noel lamented the loss of a point, but acknowledged Colorado's difference-makers.
"Duchene is a good player and MacKinnon's not a donkey, either. He's moving out there," Noel said.
The Jets were 2-for-6 on the power play and the Avalanche 0-for-2. Colorado hasn't scored in its last 24 power plays.
The Jets had also lost to Western Conference rivals St. Louis 2-1 on Tuesday. They're now 6-11-4 against their conference counterparts.
"Our division, our conference, isn't easy," Wheeler said. "There aren't any easy games.
"I think we've done a good job, we've risen to the challenge, but we've been taking positives out of losses too long. Feels like three years, come after a game like this and we say, 'Well, you know you did some good things.'
"But you've got to stay positive and you've got to draw from the positives of the game because we did a lot of really good things, but we didn't do enough to win the game and that's the bottom line."
Noel was also having a tough time focusing on the positives.
"We're a .500 team and it's not good enough," he said. "This year in the conference we are in, it won't come close. You are going to be really scrambling. We know the urgency. It has to come in our actions, not our words. Moral victories are empty."
Notes: With the win, the Avalanche equalled their most wins through 30 games in franchise history (21 in 2000-01 and 1994-95) … Winnipeg has played 20 games decided by a single goal this season and is 7-8-5 in those games … The Avs are 18-0-0 when ahead after two periods and 2-0 in shootouts this season.