Vincent Trocheck and Brandon Pirri beat Ottawa's Robin Lehner in the shootout -- Trocheck with a sharp deke and Pirri on a snap shot through the legs.
After Kyle Turris rattled a goal off the post and in, Jason Spezza fired wide on Ottawa's second chance and Luongo ended the game with a glove save on Milan Michalek's backhand while he did a split in the crease.
Luongo also made a point-blank save on defenseman Marc Methot in overtime to help the Panthers snap a three-game losing streak and win for only the third time in their last 10 games (3-6-1).
All four goals came in a 6:21 span in the second period.
Lehner had 39 saves for the Senators, who were coming off a 4-3 shootout win over Tampa Bay on Monday to snap a six-game losing streak. The had won 13 of the previous 16 meetings with the Panthers.