Jakub Voracek scored twice, including an empty-netter, and added an assist while Marc-Andre Bourdon also found the net during the outburst, which broke open a 2-2 game.
Claude Giroux chipped in with a goal and two helpers for the Flyers, who improved to 7-1-1 in their last nine games against their intrastate rivals.
With the Penguins and Flyers holding the fourth and fifth Eastern Conference playoff seeds with three games remaining, it appears likely the two squads will meet each other in the first round of the postseason.
Sergei Bobrovsky notched the win with 43 saves.
The game erupted into a brawl with 1:03 remaining after Pittsburgh's Joe Vitale leveled Flyers center Danny Briere with a hard hit. Some 46 minutes in penalties were handed out as Penguins assistant coach Tony Granato and Flyers head Coach Peter Laviolette engaged in a cross-bench shouting match.
Marc-Andre Fleury turned aside 20-of-25 shots in the setback.