After spotting the Flames a 1-0 lead, the Penguins erupted for four straight goals in the middle frame to take control of the game. Matt Niskanen, Craig Adams and Evgeni Malkin netted the other second-period markers and Jordan Stall added one in the third for Pittsburgh, which won its second straight to start the season.
Marc-Andre Fleury turned aside 16-of-19 shots to earn the victory.
The Flames' Miikka Kiprusoff stopped 32-of-36 shots.
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