Chris Davis slammed the tie-breaking three- run homer in the eighth inning, and Baltimore went on to whip San Diego, 10- 3, in the back end of a two-game interleague set.
"It was loud," said Orioles manager Buck Showalter of the blast estimated to have traveled 453 feet. "The thing about Chris is he's so lethal. He may have some bad at-bats, but he's never more than a swing away from really doing something good."
J.J. Hardy homered among his two hits and also drove in three for the Orioles, who swept the brief series and has won four of six overall.
Adam Jones collected three hits and scored twice, while Manny Machado had a pair of hits and crossed home twice as Baltimore scored seven times in the final two frames.
"We want wins. How we get them doesn't matter, who does the job, as long as we get the job done," Jones said.
Francisco Rodriguez (1-0) tossed a scoreless seventh for the win. Starter Miguel Gonzalez allowed three runs and six hits with eight strikeouts over six innings.
Jedd Gyorko's three-run shot in the sixth was all the offense for the Padres, who have dropped four of their last six.
Luke Gregerson (5-6) was charged with two runs on two hits while not recording an out in the eighth. Eric Stults had worked the previous seven frames, giving up five hits and two earned runs while fanning six.
Gregerson took over for Stults but allowed singles to Machado and Jones before Colt Hynes came in. He promptly served up Davis' go-ahead three run shot for a 6-3 Orioles advantage.
"It was a typical left-on-left situation where you're trying to throw your best pitch. Hynes left it out over the plate, and Davis is a big, strong guy," noted Padres catcher Rene Rivera.
Matt Wieters doubled, which brought on Dale Thayer, and he fanned Hardy but allowed a single to Nate McLouth and a Brian Roberts sacrifice fly which boosted Baltimore's edge to four.
The O's plated three more in the ninth to cap the rout, with Wieters posting an RBI groundout and Hardy adding a two-run single.
Hardy's two-out solo shot in the second gave Baltimore the lead, then the visitors went up 2-0 in the fourth after Machado reached on a Gyorko error and scored when Jones followed with a single which was compounded by an Alexi Amarista throwing gaffe.
The O's tacked on another in the fifth on Machado's one-out RBI single to score Steve Pearce, who led off the frame with a double, but Gyorko atoned for his earlier mistake by launching a three-run shot in the home sixth.
Chris Denorfia drew a walk and Yonder Alonso was also aboard when the ball left the yard to left center.