With the win, the Panthers (7-2) put a stranglehold on the NFC South Division and swept the season series. They won 12-9 in overtime at Tampa Bay on Sept. 14, and now own a three-game lead over the defending Super Bowl champions.
It also marked the first time the Bucs (4-5) have lost back-to-back games under Coach Jon Gruden.
Tampa Bay had rallied from a 20-7 deficit with 17 fourth-quarter points. Keenan McCardell made a one-handed touchdown reception on a 36-yard pass from Brad Johnson with 4:44 remaining.
Martin Gramatica added a 39-yard field goal with 2:41 left to increase Tampa Bay's lead to 24-20.
Delhomme lofted a 22-yard pass over the middle to Muhsin Muhammad before firing the winning touchdown to Smith. He finished 20-of-32 for 277 yards, with two touchdowns and two interceptions.