Tim Hudson allowed four runs in the first inning and the San Francisco Giants were held to three hits in a 5-0 loss to San Diego.
Alexi Amarista had three hits, including a go-ahead two-run homer, to lead the Padres to a 5-4 win over the Philadelphia Phillies.
Padres scored only run of game on Philadelphia error.
Nolan Arenado homered and Franklin Morales pitched six solid innings for his first win in two months.
Cory Spangenberg's first big league home run came on the first pitch he saw as a pinch hitter with one out in the ninth inning.
Spangenberg is the third player in Padres history to have multiple RBIs in his big league debut.
Cory Spangenberg was the team's first-round pick in 2011.
Trevor Hoffman ranks second on the all-time saves list with 601 saves, 552 of them while wearing a San Diego uniform.
Hyun-Jin Ryu came off the disabled list to pitch four-hit ball over seven innings, and Matt Kemp singled in the go-ahead run.
Petco Park did not fare too well on the list.
Rene Rivera tied the game with a home run in the ninth inning, then won it with an RBI single in the 10th inning.
Tyson Ross pitched 6 1-3 strong innings, Abraham Almonte had two RBIs and the San Diego Padres beat Milwaukee 4-1.