The Sabres owned a 2-0 lead after the opening period, and then fell victim to an avalanche of goals that made for the Flyers' largest offensive output in more than four months. Philadelphia's biggest goal total of the season came Nov. 5 in a 9-2 win over Columbus.
Philadelphia snapped a two-game skid and handed Buffalo its third straight loss.
Talbot began the surge by tipping in a shot 54 seconds into the middle period. Simmonds then scored two power-play goals 3:17 apart to drive starting goaltender Jhonas Enroth from the game.
Ilya Bryzgalov, making his first start since Feb. 7, benefited from the outbreak of goals and made 27 saves to get the win.