Venable's third game-ending hit drove home Chris Denorfia from third to complete an improbable comeback after the offense struggled mightily through the first eight innings.
Kyle Blanks forced extras in the bottom of the ninth with a one-out sacrifice fly off Mariners closer Tom Wilhemsen, who blew his second save in 13 tries by allowing just his second earned run in 23 innings.
The dramatic finish followed a home run from Jason Bay off Padres closer Huston Street that gave Seattle a 2-1 lead in the ninth. Street has given up seven home runs in 20 1-3 innings this season.
Stults was dominant in his best start of the season. He allowed one run on three hits in eight dominant innings before Street took him out of the decision.
The left-hander struck out hitters in bunches, including two stretches of four straight. Stults' previous strikeout best was nine, set on Aug. 17, 2007 while pitching for the Los Angeles Dodgers against the Colorado Rockies.
Mariners starter Joe Saunders continued his dominance over the Padres with one run and four hits allowed in seven strong innings, but his bullpen let him down. Saunders has allowed just one run in his last 29 2-3 innings against the Padres.
Chase Headley opened the scoring with a 403-foot solo home run to left field in the first inning.
Saunders kept the Padres off balance with a mix of pitches and a well-placed fastball, and pitched 6 1-3 shutout innings after Headley's blast.
The Padres got to Seattle reliever Yoervis Medina (1-1) to win it in the 10th. Denorfia legged out an infield hit and advanced to third on Everth Cabrera's seeing-eye bloop single near second base. Headley was intentionally walked.
Luke Gregerson (3-2) pitched a scoreless 10th to earn the win.
NOTES: Stults is just the third Padres pitcher to record 12 strikeouts without issuing a walk ... Headley's fifth homer of the season ended Saunders' scoreless streak against the Padres at 22 2-3 innings.