Joe Vitale scored his first NHL goal on a wrister set up by Brett Sterling and Paul Martin with 2:33 left in the first period, giving the Pens a 1-0 lead.
Colorado tied it early in the second period when Chris Stewart got a wrist shot past Marc-Andre Fleury who had 29 saves for the night.
Cameron Gaunce gave the Avalanche a 2-1 lead at 14:19, before Jordan Staal tied it about 30 seconds later with assists from Nick Johnson and Kris Letang.
Pittsburgh killed back-to-back penalties late in the second period, including a brief 5-on-3 advantage that lasted 38 seconds.
Both teams were held scoreless in third period. Tyler Kennedy broke the tie when he scored a power play goal 4:10 into overtime.
Kennedy knocked in a rebound after a shot from Alex Goligoski bounced to him off the pads of Avs goalie Peter Budaj. Kevin Porter was called for tripping moments before Kennedy’s 12th goal of the season.
The Pens outshot the Avalanche 36-31.
Both teams have had their share of adversity in recent weeks with their ranks decimated by injuries and suspensions.
Sidney Crosby remains out indefinitely because of a concussion, while Evgeni Malkin is done for the season due to a knee injury. Forwards Arron Asham, Mike Comrie, Chris Kunitz, Mark Letestu and Eric Tangradi are also sidelined.
On Wednesday, hard hitter Matt Cooke served the last of a four-game suspension. Eric Godard also sat out the second of a 10-game ban for leaving the bench to join a fight against the New York Islanders last week.
The Avalanche were without leading scorer Matt Duchene, who is sidelined indefinitely after hurting his hand in a 9-1 loss to Calgary on Monday.
This was the latest blow to a reeling squad that is missing captain Adam Foote (leg) for at least another week and T.J. Galiardi (forearm) for possibly two months.