James Neal and Jarome Iginla each scored twice, and Kris Letang had four assists, as the Penguins took a 3-1 lead in their best-of-seven semi-final series.
The Penguins, who finished the regular season as the East's top seed, will have the chance to seal the series in Game Five in Pittsburgh on Friday.
The seventh-seed Senators took a 2-1 lead after the first period, goals from Milan Michalek and Kyle Turris sandwiching Neal's first of the night.
The Pens then erupted for six straight goals with Chris Kunitz leveling the score at 2-2 and Iginla putting Pittsburgh in front 3-2 in the second period.
Pascal Dupuis and Sidney Crosby joined Neal and Iginla on the third period scoresheet as the Penguins threatened to run riot at a stunned Scotiabank Place.
Ottawa captain Daniel Alfredsson netted late in the third period. He also assisted on Michalek's shorthanded opener and has reached the 100-point milestone for his postseason career.
- Ice Hockey
- Sports & Recreation
- Jarome Iginla
- The Penguins
- James Neal
- Milan Michalek
- Kris Letang