Gary Roberts had two goals in the opener of the Eastern Conference quarterfinal series. The second-seeded Penguins shut out a playoff opponent for the first time in seven years.
Martin Gerber allowed all four goals on 35 shots. The second game of the series will be played in Pittsburgh Friday.
Roberts scored just 68 seconds into the game off a feed from behind the net by George Laraque. Petr Sykora scored on a two-on-one break at 7:32 of the first period.
The Senators failed to score on a two-man, 57-second advantage late in the second period and Pittsburgh put the game away when Evgeni Malkin tallied with 6:02 left in regulation.
Ottawa defenseman Anton Volchenkov was struck in the face by the puck with 9:26 left in the second period and did not return.
The Senators eliminated Pittsburgh in five games in the opening round last year.