Boston rookie Eduardo Rodriguez retired the first 10 Baltimore batters, then struggled to get anyone out during a very long fourth inning.
The Orioles tagged Rodriguez for seven hits and six runs in the fourth inning and held on for an 8-6 victory over the Red Sox on Thursday.
Boston manager John Farrell said the inning fell apart quickly once Baltimore got a base runner and Rodriguez stopped throwing from his windup.
"He's cruising along. He retires the first 10 of the game. He was dominant," Farrell said. "Then he gets in the stretch, they make a little bit of an adjustment and he's not commanding the baseball as he was."
Rodriguez (3-2) allowed six runs and seven hits after allowing one run or none in four of his first five major league starts.
Matt Wieters hit a two-run homer during a six-run fourth inning and J.J. Hardy added a two-run double against Rodriguez, who lasted just 3 2-3 innings.
"He was pretty good in his first time around facing those guys, then obviously they made the adjustments that they needed," Boston shortstop Xander Bogaerts said.
Steve Pearce had three hits for Baltimore, which took two of three in the series and bounced back after Wednesday's loss to beat Boston for the seventh time in eight games.
Alejandro De Aza hit a three-run homer for the Red Sox and Bogaerts had a pair of doubles and drove in a run Thursday.
Miguel Gonzalez (6-4), activated before the game following a stint on the disabled list with a strained right groin, allowed four runs and eight hits in five-plus innings.
Zach Britton gave up a leadoff single to Jackie Bradley Jr. in the ninth, then got three straight outs for his 21st save in 22 chances.
Baltimore scored the tying run in the fourth when Rodriguez's throwing error on Nolan Reimold's infield hit allowed Chris Parmelee to score.
Wieters homered into Boston's bullpen on a 2-0 pitch for a 3-1 lead, starting a streak of five straight hits for the Orioles that included Hardy's double off the Green Monster. No. 9 hitter Ryan Flaherty chased Rodriguez with a sacrifice fly.
De Aza's fourth-inning homer hooked around the Pesky Pole.
Manny Machado hit a run-scoring single in the sixth off Jonathan Aro, who made his major league debut, and Chris Davis made it 8-4 with an RBI double in the seventh.
The Red Sox were without second baseman Dustin Pedroia, who went on the 15-day DL after straining his right hamstring Wednesday.
"That's really tough. That's the fire of our team," Bogaerts said. "Replacing Dustin isn't easy. It's definitely a hard hit for us."
The Red Sox recalled Jackie Bradley Jr. and started him in right field, where he saved a run in the ninth by catching a shallow fly ball on the run, then delivered a strike to the plate in time to get David Lough at home after he tagged from third.
Bradley also had a pair of hits, ending an 0-for-30 streak that dated back to last season.
"His defense has always spoken for itself," Farrell said. "Hopefully this is a chance for him to jump-start some confidence and feel as though he belongs."
Orioles: CF Adam Jones missed his seventh game in Baltimore's past nine because of an injured right shoulder.
Red Sox: LF Hanley Ramirez missed the game after bruising his left hand Wednesday. "He's swollen and got some soreness," manager John Farrell said.
Orioles: LHP Wei-Yin Chen (3-4) is slated to rejoin the rotation on Friday when the Orioles open a three-game series against Cleveland and RHP Corey Kluber (3-9).
Red Sox: RHP Rick Porcello (4-8, 5.61 ERA), who has lost six straight starts since winning at Seattle on May 16, is scheduled to start Friday against the Rays and RHP Alex Colome (3-3).