Volquez (3-6) was in command all night, allowing one run and four hits in 6 2-3 innings. He struck out six and walked four while sending Seattle to its fifth consecutive loss.
Converted reliever Erasmo Ramirez (0-1) took the loss in his first start for the Mariners. He threw five innings, allowing eight hits and six runs -- five earned. He struck out three and walked one.
In an interleague matchup of last-place teams, Padres starters yielded only two earned runs in three games at Seattle.
San Diego put together four singles to score three runs in the third. Chris Denorfia led off with an infield single, then Jesus Guzman blooped a hit to right.
John Baker was trying to put down a sacrifice bunt, but it turned into a single when Ramirez did not commit off the mound. Third baseman Kyle Seager ran to cover third, and shortstop Munenori Kawasaki sprinted to second. The ball just rolled out to shortstop, and everyone was safe.
Kawasaki made a leaping grab of Alexi Amarista's liner to temporarily stem the rally, but Will Venable singled crisply to right, the first hard hit of the inning, to score Denorfia.
Everth Cabrera followed with a grounder to Seager, who threw to second. Second baseman Dustin Ackley tried to turn a double play, but threw low to first. Guzman scored on the fielder's choice and Baker came in on Ackley's throwing error when the ball skidded past Justin Smoak.
The Padres chased Ramirez with three consecutive hits to open the sixth. Carlos Quentin and Yonder Alonso singled, and Denorfia doubled to score Quentin. Hisashi Iwakuma replaced Ramirez and allowed a single to Guzman. That was Iwakuma's only batter faced, and he threw just two pitches.
Charlie Furbush took his place. Hitters were 0 for 32 against Furbush in his last 11 1-3 innings before Baker and Amarista hit back-to-back singles. Furbush struck out Venable and Cabrera to end the inning with San Diego ahead 6-0.
Volquez sailed through the first five innings, allowing only one hit. Ramirez was right with him following a 28-pitch first. Cabrera had a 13-pitch at-bat in the first to earn a walk, raising Ramirez's pitch count early.
But Ramirez zipped through the second, third and fourth, allowing just a leadoff single in the second before retiring nine consecutive batters.
Ackley singled in the seventh to drive in Franklin Gutierrez and snap Seattle's 15-inning scoreless streak. Gutierrez made his season debut Thursday after recovering from a partial right pectoral tear followed by plantar fasciitis. In his first at-bat, he was hit by a pitch from Volquez.
Gutierrez finished 1 for 2 and drove in a run in the eighth.