Matt Wieters knocked in the winning run in the ninth inning, as Baltimore clipped Boston, 3-2, in the opener of a three-game series from Fenway Park.
Chris Davis clubbed his team-record 51st home run and Brian Roberts added an RBI for the Orioles, who have won three of their last four.
"I think the biggest thing for me is to go out there and continue to have quality at-bats and do what I can to help the team win," Davis said.
Tommy Hunter (6-4) recorded the final two outs of the eighth, while Jim Johnson tossed a scoreless ninth for his 46th save. Scott Feldman walked a career-high six batters over his five-inning start, but allowed just two hits and one earned run.
Dustin Pedroia homered and Xander Bogaerts drove in the other run for the Red Sox, whose three-game win streak was snapped but whose magic number to clinch the AL East was reduced to three after Tampa Bay lost to Texas.
Koji Uehara (4-1) served up the lead run in the ninth. Ryan Dempster worked six full frames, giving up two runs on three hits with five strikeouts and four walks.
Uehara entered the ninth having retired the last 37 batters faced, but Danny Valencia ended that streak by greeting the Japanese right-hander with a triple to deep center. Pinch-runner Alexi Casilla then scored on a line drive to right from Wieters for a 3-2 Orioles edge.
Johnson locked up the win by fanning Bogaerts, stranding a runner on second.
Pedroia began the home first with a blast over the Green Monster.
Boston added one more in the fourth. Jarrod Saltalamacchia reached when O's third baseman Manny Machado flubbed his grounder, then Stephen Drew walked and both men advanced on a double steal. Baltimore left fielder Nate McLouth dropped a sinking liner from Bogaerts to score one run, but Pedroia grounded into an inning-ending 5-4-3 double play.
Baltimore halved its deficit in the fifth, as Valencia worked a leadoff walk, moved to third on a one-out J.J. Hardy double and scored on a Roberts grounder.
Davis crushed his milestone homer to dead center in the sixth which tied the game, 2-2. He bested the previous record of 50, previously held by Brady Anderson since his breakout 1996 campaign.
Brandon Workman was lifted after allowing a single to McLouth and double to Machado to begin the eighth. Craig Breslow retired the next two batters on grounders to a drawn-in infield and got Nick Markakis on a fly to left to end the frame.
Baltimore has taken eight of 14 meetings with Boston, including four of seven in the Hub ... The Red Sox swiped three bases on Tuesday, upping their team mark to 35 straight attempts without being caught ... White Sox closer Bobby Jenks still holds the MLB record for relievers with 41 straight batters retired ... Prior to the contest, the Red Sox recalled infielder Brock Holt and pitchers Brayan Villarreal and Steven Wright from Triple-A Pawtucket, while the O's activated outfielder Steve Pearce from the 15-day disabled list.