Jason Pominville scored for Buffalo to start the shootout, but the Sabres could not put another one past Jakob Markstrom. Jonathan Huberdeau tied it for the Panthers in the second round and Santorelli ended it by putting a wrist shot over prone goaltender Ryan Miller.
Florida had lost its previous three games. The win was only the 10th of the season for the Panthers, who have the worst record in the NHL.
Marcus Foligno put Buffalo in front 4-3 by scoring on the power play with 8:27 left in the third period. Huberdeau tied it with 6:09 to go.
Markstrom stopped 36 shots in the victory. Miller also made 36 saves in what was Buffalo's second loss in a row.