Alexi Amarista and Chris Denorfia opened the 13th with singles off Jose Mijares (0-1), with Amarista ending up on third. The Padres then turned to Amarista, the scheduled starting pitcher for Tuesday, and he executed a squeeze play, slapping the ball to the left of the mound for a run-scoring single.
After an out Mijares gave up a single that loaded the bases and was lifted for Jake Dunning but, after getting the second out, Dunning walked Yasmani Grandal, forcing in the final run.
San Diego Manager Bud Black, who collected his 500th managerial win in the game, said he went with Amarista because "we ran out of (position) players."
Nick Vincent (1-0) pitched two innings of one-hit relief for the win and Huston Street, despite giving up a single, picked up his 14th save.
The Padres broke on top with back-to-back doubles by Edinson Volquez and Chris Denorfia in the third inning but San Francisco scored three times in the fourth with a rally that started with a walk and included four hits and a sacrifice fly.
Grandal scored on a wild pitch in the sixth and Chase Headley singled in Denorfia in the seventh, pulling San Diego into a 3-3 tie.