The two teams engaged in a scoreless battle for most of the first period.
Colorado’s Matt Duchene finally opened the scoring with 26 seconds left, notching his ninth of the season on a power play, assisted by Jarome Iginla and Tyson Barrie. The Avalanche carried their 1-0 lead into the second period, before things changed suddenly.
Five minutes into the second, winger Beau Bennett won a draw and fed the puck to the left point, where defenseman Ian Cole fired a slap shot that deflected off David Perron and past Colorado goaltender Reto Berra to tie the game.
Less than 90 seconds later, with the Penguins on the power play, Kris Letang passed from the center point to Evgeni Malkin high in the right circle. Malkin fired the puck past Berra on a one-timer that gave Pittsburgh the lead.
The Penguins barrage continued when Berra went behind his net to handle a dump-in, but Chris Kunitz knocked the puck away. Nick Bonino got the puck in front of the net and Kunitz back-handed it onto the net to make it 3-1.
The lead stood up into midway through the final period, when Tyson Barrie scored his first of the year on a feed from Iginla to pull Colorado within one at 3-2.
Three minutes later, Sidney Crosby got behind the Colorado defense and took a pass from Pascal Dupuis before tossing a backhander between Berra’s legs to double the lead.
With a little more than a minute left and Berra off in favor of an extra attacker, Duchene scored his second of the game on assists from Gabriel Landeskog and Mikhail Grigorenko.
Fleury stopped 28 of the 31 shots he faced, while Cole had two assists for Pittsburgh.
Barrie had two points for Colorado and Iginla added a pair of assist.
Pittsburgh continues its four-game homestand Saturday against San Jose.