After issuing two walks to open the seventh in a 5-0 game, Sale (6-4) was lifted by manager Alex Cora. As he was making his way to the dugout, the left-hander yelled at home plate umpire Brian Knight and was promptly ejected.
It was the second career ejection for Sale, the other coming in April 2015 when he was with the White Sox.
Sale struck out nine, allowed one run and gave up two hits in ending a run of three straight losing starts.
Mookie Betts and J.D. Martinez homered for the Red Sox, who are 9-1 against the Orioles this season.
Baltimore has lost seven straight and 14 of 16.
Betts, the major league leader in batting average, came off the disabled list Monday after missing 14 games with an abdominal strain. He played Monday, was rested Tuesday and returned to the top of the lineup in the series finale.
Betts hit a 3-2 pitch from Yefry Ramirez over the center-field wall in the third for his 18th home run. A three-run fifth made it 4-0, and Martinez hit his team-leading 22nd homer in the seventh.
After placing Andrew Cashner (back) on the disabled list Tuesday, the Orioles recalled Ramirez from Triple-A Norfolk to make his major league debut. The 24-year-old left with the score 1-0 in the fifth, but Mike Wright allowed both inherited runners to score.
Ramirez (0-1) gave up three runs and four hits over 4 1/3 innings, striking out six.
Baltimore got its lone run in the seventh, when Jace Peterson hit a sacrifice fly soon after Sale departed.
Red Sox: Cora said LHP Drew Pomeranz's neck is sore and that the club would not plan for his return until after a weekend series in Seattle. Pomeranz originally went on the DL on June 5 with biceps tendinitis. ... 2B Dustin Pedroia (left knee) has been doing some weight lifting but is staying away from baseball activities for now, Cora said.
Orioles: Orioles reliever Richard Bleier, one of the better performers on a ragged team, clutched his shoulder after throwing a pitch in the eighth inning and was immediately removed from the game. His status was not immediately known. Bleier is 3-0 with a 1.93 ERA over 31 appearances. ... IF Tim Beckham (core muscle surgery) will begin a rehab assignment at Double-A Bowie on Friday, manager Buck Showalter said.
Red Sox: LHP David Price (7-4, 4.00 ERA) seeks his sixth straight win when Boston faces Mariners ace Felix Hernandez in the opener of a four-game series at Seattle.
Orioles: After taking Thursday off, Baltimore opens a three-game series against the visiting Miami Marlins in a matchup of last-place clubs.
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