PITTSBURGH -- Colorado captain Gabriel Landeskog tied the score with a power-play goal in the third period, then batted in a deflected Nathan MacKinnon shot 22 seconds into overtime as the Avalanche dealt the Pittsburgh Penguins their first loss of the season, 4-3 Monday night.
MacKinnon's shot from the middle of the ice glanced off Penguins defenseman Kris Letang, allowing Landeskog to deftly knock it past goalie Marc-Andre Fleury, who made 27 saves.
Avalanche backup goalie Calvin Pickard gave up two quick scores midway through the first period but limited the Penguins to just one more goal, by Trevor Daley midway through the third, while making 28 saves.
Pittsburgh (2-0-1) won its previous two games while starting its defense of the Stanley Cup. Colorado improved to 2-0-0 under new coach Jared Bednar, who wasn't hired until two months ago.
Phil Kessel scored on the power play and teamed with Matt Cullen to give Pittsburgh a two-goal lead with a pair of quick goals midway through the first period. Colorado came back later in the period with goals by Jarome Iginla on the power play --the 612th goal of his career -- and Patrick Wiercioch only 1:23 apart.
Iginla scored during a two-man advantage, but Pittsburgh killed off another Avalanche five-on-three in the third period, and building off that momentum, made it 3-2 on Daley's power play goal at 9:12. Colorado was 2-for-6 and Pittsburgh was 2-for-5 with the man advantage.
Daley's slap shot from the left point eluded Pickard to the glove side as center Scott Wilson screened him in front at 9:12 of the third, just over two minutes after an Evgeni Malkin goal was waved off because Malkin interfered with Pickard while skating through the crease. Daley missed the Stanley Cup finals last season due to a broken leg.
However, the Avalanche converted with the man advantage themselves just over three minutes later as Landeskog steered a shot through a small opening between Fleury's left shoulder and the goal post for his first of the season.
His second of the season won it.
The Penguins, coming off a pair of one-goal wins in their first two games, needed only a 36-second span of the first period to open up a 2-0 lead for Fleury, who is back in net as Stanley Cup star Matt Murray heals from a broken hand.
Kessel, whose regulation goal and shootout score decided the Penguins' first two games, beat Pickard between the pads with a wrist shot from the edge of the left circle for a power-play goal 8:57 into the first. Defenseman Nikita Zadorov was off for cross checking.
Cullen, filling in for Sidney Crosby (concussion) as the Pens' top-line center, made it 2-0 by scoring off his own rebound in front at 9:33.
But the Avalanche, trying to avert the slow starts that doomed their last two seasons, answered later in the first period after the Penguins drew three penalties in just over four minutes.
Jarome Iginla got his first of the season with five seconds left on a two-man advantage, taking Nathan MacKinnon's pass from the goal line to throw a wrist shot past Fleury from the right circle at 16:27.
The Avalanche didn't score on their remaining 54 seconds of power play time, but Wiercioch teed up a shot from beyond the circles that threaded its way through traffic and past Fleury at 17:50, Colorado's second goal in a span of 1:23 -- and Wiercioch's 13th in 213 career games.
NOTES: Penguins C Sidney Crosby (concussion), G Matt Murray (broken hand) and F Bryan Rust each missed their third consecutive game. Crosby and Murray skated together before the team's morning skate. Coach Mike Sullivan said Murray and Rust are close to rejoining practice, and that Crosby is progressing. ... C John Mitchell (hip) did not accompany the Avalanche on their four-game road trip that continues Tuesday night in Washington, when former Capitals G Semyon Varlamov returns to net. He gave up five goals to Dallas on Saturday. ... The Penguins play their first back-to-back of the season Tuesday night at Montreal, which is also their first road game. ... Colorado scratched Mitchell, D Eric Gelinas and LW Cody McLeod. Pittsburgh withheld D Derrick Pouliot, Crosby and Murray.