Aaron Harang (3-0) allowed one run on three hits and one walk while fanning eight in six innings for the Padres.
Michael Bourn went 2-for-4 with a run scored and a stolen base for Houston.
J.A. Happ (1-2) gave up four runs on seven hits and two walks. He also struck out three in a losing effort.
The Astros will attempt to get back on track Saturday evening against the Padres in the third game of the four game set. Fifth start Nelson Figueroa (0-2, 10.61) will take the hill against Padres ace Matt Latos (0-1, 4.50). The Padres will be looking to get back to .500, while the Astros will be trying to clinch a non-losing series for the first time all season.