Jesus Guzman went 2-for-3 with a solo shot and an RBI double, while Yasmani Grandal drove in a pair for the Padres.
Chris Denorfia added three hits and scored twice for San Diego.
Eric Stults (8-3) earned the win, holding the Giants to three runs on six hits over six innings.
Madison Bumgarner (16-11) was reached for five runs (four earned) on four hits over four innings for National League West champion San Francisco.
Hunter Pence smacked a three-run homer for the losers.