Volquez (3-6) struck out six and walked four for the Padres, who swept the Mariners in three games and have won four of their last five after a three-game losing streak.
The Padres jumped out to a 3-0 lead in the fifth, when Denorfia scored on a bases-loaded single by Will Venable, Guzman came in on a fielder's choice and John Baker scored on a throwing error by Dustin Ackley.
San Diego added three more in the sixth, when Carlos Quentin scored on a double by Denorfia, Yonder Alonso came in on a single by Guzman, and Denorfia came in on Baker's one-out single.
Mariners starter Erasmo Ramirez (0-1) gave up six runs -- five of them earned -- on eight hits over five innings, walking one and striking out three.
Video of Victoria’s Secret models trying to 'twerk' hits Instagram
Costly malfunction causes beer flood at Boston-area brewery