David Ortiz had a solo homer and two hits for the World Series champion Red Sox, who have won three of four.
Nelson Cruz had a pair of run-scoring singles for the Orioles, who had a three-game winning streak halted.
Junichi Tazawa (1-0) pitched 1 1-3 hitless innings of relief. Koji Uehara struck out three after a leadoff walk for his fourth save.
The benches emptied briefly in the seventh after Bud Norris (0-2) threw high and tight to David Ross, who was trying to sacrifice. Ross yelled something, but Orioles catcher Matt Wieters stepped in between and both sides retreated to the dugouts.
Baltimore benefited from a challenge that overturned a call at first on what would have been Cruz's inning-ending grounder in the sixth.
Holt tripled into the right-center field gap in the seventh after Mike Carp drew a leadoff walk from Norris. Herrara then dropped down a bunt fouling off on his first attempt.
Boston starter Felix Doubront retired 13 consecutive batters after giving up a run in the first before Nick Markakis opened the sixth with a single. He was erased when Delmon Young bounced into double play.
The Orioles then got runners on first and third when Cruz hit a grounder to deep third. Holt made a throw from near the foul line. Cruz was called out by first base umpire Ted Barrett. Manager Buck Showalter challenged his first call of the season and it was overturned after a 49-second wait.
Ortiz's homer hooked around the Pesky Pole and gave the Red Sox a 2-1 lead in the fourth.
Doubront pitched 6 2-3 innings, allowing two runs on five hits, striking out seven and walking two.
Cruz's RBI single made it 1-0 in the first.
Boston tied it in the bottom half when third baseman Jonathan Schoop misplayed a probable inning-ending, double-play grounder.
The Orioles, who set a major league record for fewest errors last season (54) and errorless games (119), have committed just four this season - all of them by a third baseman filling in for Gold Glove winner Manny Machado, who is recovering from offseason left knee surgery.
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