Chris Drury's game-winner leads Sabres to 4-2 win over Penguins
Brian Campbell and Adam Mair also scored for the Sabres (5-1). Michel Ouellet and Ryan Malone scored for the Penguins (2-2-3).
The Penguins played without Sidney Crosby, John LeClair, Mark Recchi and Sergei Gonchar. Buffalo played most of its starters with the exception of Jochen Hecht, who is nursing a groin injury.
Marc-Andre Fleury made 25 saves for the Penguins.
The Sabres will open the regular season on Wednesday night in Carolina against the Hurricanes in a rematch of last season's Eastern Conference finals. The Penguins will open at home against Philadelphia on Thursday night.