In the process, the Penguins clinched an Eastern Conference playoff berth and also reclaimed sole possession of first place in the Atlantic Division, at least for a few hours.
The Flyers, meanwhile, watched as their tenuous hold on an Eastern Conference playoff berth got a bit more slippery.
Chris Kunitz also scored as Pittsburgh took a two-point over New Jersey, which plays later Saturday in Montreal. Marc-Andre Fleury finished with 26 saves and also added his first point of the season, assisting on the Kunitz goal.
"You always want the 'X' by your name (in the standings)," Penguins coach Dan Bylsma said. "We want to finish as high as we can, but when you have the 'X' by your name you know you're going to the postseason."
Arron Asham scored just 62 seconds after the opening faceoff to get Philadelphia off to a fast start, but the Flyers slipped into a tie with the Bruins for the final two playoff spots in the East. They are just four points ahead of the ninth-place Thrashers, who play Saturday night in Carolina.
"I don't think it's an easy situation, we're a team that's struggling right now," Flyers forward Simon Gagne said. "You come here and play against a team like Pittsburgh that we all know has a lot of success against us."
Johan Backlund got the start and made his NHL debut for the Flyers. He stopped 22 of 24 shots before veteran Brian Boucher replaced him to begin the third period. Backlund left the game with an unspecified lower-body injury -- the team already has goalies Ray Emery (hip surgery) and Michael Leighton (high ankle sprain) on the shelf.
After Asham scored early in the first on an attempted pass that Fleury misplayed, Kunitz answered with 58 seconds left in the period to draw the Penguins even. They went ahead to stay when Dupuis scored the only goal of the second, a backhander that beat Backlund at the 6:03 mark.
"It was a tough start on that play, but I tried to forget about it," Fleury said. "I knew with the guys that we have that we could come back and they did a great job all game long."
With Boucher on in relief, Cooke scored off a nice backhand feed by Fedotenko at 7:32. Then, Fedotenko closed the scoring at 14:31 off Crosby's third helper of the game.
"All of our goals were a result of going to the net, crashing there and getting second chances," Bylsma said. "That's what you have to do. We played in the offensive zone for long periods, but it wasn't perfect and we can get better."
Once again, Pittsburgh played without sniper Evgeni Malkin (foot) and power-play quarterback Sergei Gonchar (illness). Both will be game-time decisions Sunday when the Penguins host the Maple Leafs.
"We're trying to get back on track here," Crosby said. "We think we can play better hockey. We're missing Gonch and Geno, so it doesn't get any easier, but today was intense and we wanted that."
This was also the final regular-season game between the two Atlantic rivals at Mellon Arena, formerly known as Civic Arena and affectionately termed "The Igloo." The Penguins move into the brand-new Consol Energy Center next fall.
Material from wire services and team broadcast media was used in this report.