BOSTON -- The first pitch of the game set the tone for José Berríos' night.

Seconds after the Twins starter released a 93.7-mph fastball, Red Sox leadoff batter Mookie Betts fired a home run a Statcast-projected 348 feet out of Fenway Park.

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The following inning, Betts again jumped all over the first pitch he saw from Berrios. He rocked a 81.8-mph curveball to left-center field again, this ball sailing a projected 438 feet out of the stadium and driving in three runs.

After the deja vu matchup, the Twins were in a hole they couldn’t climb out of in a 6-2 loss on Wednesday night.

“The two homers were early in the game, obviously, first few innings,” Berrios said. “After that, I felt like I made adjustments and tried to keep my team in the game, tried to battle and come back.”

Berrios thought the Red Sox were being aggressive early as part of their game plan. He was right: Manager Alex Cora pointed out Berrios tries to get ahead in the count, and Boston focused on countering that.

“I just know he’s a good pitcher,” Betts said. “You start falling behind him, he’ll put you away quick.”

Berrios chalked up Betts’ two home runs to the reigning American League Most Valuable Player Award winner getting the better of him this time around. Berrios pointed to their last matchup on June 17, when he threw eight innings and allowed just one run. In that game, Berrios held Betts to a single. Betts entered Wednesday's game batting .308 (4-for-13) against Berrios.

“In reality, the last time I faced him, I dominated him, and today it was his day,” Berrios said. “He obviously beat me the first two pitches, and they got the win today. He looked very good at home plate, and obviously he was feeling good at home plate.”

Berrios’ 100th career appearance (99th start) was marred by six runs on eight hits and three walks over five innings. He also struck out six**,** passing Bert Blyleven with the most strikeouts (559) by a Minnesota pitcher through his first 100 career games.

“Jose threw the ball well, missed some bats,” Twins manager Rocco Baldelli said. “Was it probably his best start as far as execution on the year? No, but I thought he threw plenty good enough to keep us in the game. When Mookie comes up and hits a three-run bomb on a first-pitch breaking ball, you kind of do have to tip your cap to him.”

This wasn’t the first time Berrios surrendered two home runs to the same player in a game this season. The Rangers’ Danny Santana did the same damage to Berrios in the first and second innings on Aug. 17.

Minnesota will need its ace right-hander to channel his first-half efficiency as the club eyes the playoffs. After going 8-2 through June 6, Berrios is 3-6 in 14 starts since. He is coming off an August in which he posted a 7.57 ERA and went 1-3 in five starts.

“He’s put us in spots to win, I’d say, the majority of games he’s pitched in,” Baldelli said. “He’s thrown the ball well, and not just kept us in the game, but pitched us into a really good spot to win. As of late, has he been as crisp? No. And has he missed some spots? Absolutely. It feels like when he has missed his spots, we’ve unfortunately gotten burned on some of those pitches, and you end up with some situations where you’re looking at a three-run home run, say, or situations like that. That’s happened a few times in the second half.”

With the loss -- only their second in 11 games -- the Twins are 5 1/2 games ahead of the Indians in the AL Central. They are 2-3 against the Red Sox this year, and they wrap up the season series on Thursday.