Jonathan Huberdeau accounted for a goal and an assist, and Jesse Winchester, returning from hand injury, assisted on three scores as the Panthers dealt Pittsburgh its first home loss since Nov. 13.
Dmitry Kulikov and Shawn Matthias also scored.
Scott Clemmensen, making his first start since Dec. 29, turned aside 35-of-36 shots for Florida, which snapped a two-game skid.
Matt Niskanen got the Penguins' only goal.
Marc-Andre Fleury allowed five goals on 28 shots.