Volquez (4-7) scattered four hits and overcame three walks through 6 2/3 scoreless frames. He struck out four while placing 67 of his 115 pitches for strikes.
Joe Thatcher and Luke Gregerson combined to blank the Mariners over 1 1/3 innings and Huston Street collected his 10th save with a 1-2-3 ninth for the Padres, who took two of three in their series at Petco Park.
San Diego scored both its runs on Alexi Amarista's ground rule double in the fourth inning.
Mariners starter Hector Noesi (2-9) was the loser, despite surrendering a stingy two runs on seven hits over six innings.