Nathan Gerbe scored and set up Drew 2 victory over the Penguins.
Jhonas Enroth made 30 saves for Buffalo, which rebounded from Friday's home loss against Carolina. Enroth stopped 13 shots in the third period and held steady in a pressure-packed final few minutes.
James Neal and Jordan Staal had the goals for Pittsburgh, which swept the four-game series against Buffalo last season. The Penguins hadn't lost to the Sabres at home since December 8, 2008, when they were still playing at Mellon Arena.