Pittsburgh boosted its lead over the Senators in the Eastern Conference semifinals to 3-1 and will try to close out the series when it hosts Game 5 on Friday.
Ottawa took a 2-1 lead after one period, then melted away while the Penguins were bombarding Ottawa goaltender Craig Anderson.
Chris Kunitz lifted the Penguins into a tie 1:08 into the second period and Iginla put Pittsburgh in front to stay 40 seconds later with a deflection.
The Senators still trailed by just one heading into the third, but Pittsburgh added four goals during the opening 9:53 of that period. The last of them came from Iginla on the power play.
Vokoun's only setback in the postseason came when he took a shutout into the final minute of Game 3 against Ottawa and wound up suffering the loss in double overtime despite making 46 saves.
Anderson gave up six goals on 38 shots before being replaced by Robin Lehner.