Vance Worley even turned in his best start of the season.
But the opportunistic Red Sox pieced together a late rally, with one run in the seventh inning and another in the 10th inning against the Minnesota bullpen.
Jonny Gomes hit a sacrifice fly in the 10th to lift the Red Sox to another comeback victory, 3-2 over the Twins on Friday night.
"We knew coming in Buchholz was going to be tough. And he was. Our guys did the best we possibly could with it," Twins manager Ron Gardenhire said. "We had a couple of chances and missed adding on some more runs. We just didn't do enough."
The Red Sox have won three straight after losing 10 of their previous 14 games, while the Twins have lost three in a row after winning six of nine. Boston retired 17 batters in a row to finish the game, starting with Josh Willingham in the fifth.
The struggling slugger took a called third strike for the second out of the inning after Buchholz gave up two singles and a walk to load the bases.
"There was nowhere else to put him, so you've got to throw strikes," Buchholz said.
Then Justin Morneau, whose 11-game hitting streak ended, flied out to left field at medium depth.
Twins reliever Josh Roenicke (1-1) gave up a single and a walk to open the 10th. After a rare sacrifice bunt by Will Middlebrooks, Stephen Drew was intentionally walked to load the bases. Then Gomes sent a drive to center field, where Aaron Hicks caught the ball but double-clutched on his throw and didn't have a chance to get the speedy Dustin Pedroia. Hicks bumped into left fielder Oswaldo Arcia, ruining his rhythm.
"Hicksy was calling the ball and I don't think Arcia heard him because he was concentrating on catching the ball," Gardenhire said. "I would like to have seen Hicks not make contact and see what kind of throw, because he's got a cannon."
Alex Wilson (1-0) picked up the victory by getting the last out of the ninth and Koji Uehara threw a perfect 10th for his first save, with closers Joel Hanrahan and Andrew Bailey both on the disabled list. The night before at Tampa Bay, Middlebrooks hit a three-run double in the ninth to give Boston a 4-3 win.
Pedro Florimon hit a two-run homer off Buchholz, just the second time the right-hander was taken deep this season.
Buchholz struck out nine batters over seven innings, including five in a row spanning the first and second frames, but he was stuck with a no-decision for the third straight start. Buchholz's ERA, second-lowest among American League qualifiers, actually rose nine points to 1.78.
Florimon also had a hand in three double plays induced over six innings by Worley, who gave up just one unearned run on an RBI single by David Ortiz. The shortstop made a slick pivot and quick throw to end the third and the fifth on grounders hit by Pedroia.
Florimon had a chance to start a fourth, with Brian Duensing pitching in the seventh, but Jacoby Ellsbury's sharp bouncer glanced off his glove as he tried to make a sliding stop. The ball rolled into center field for a single, and Gomes—who led off with a walk—scored to tie the game at 2.
With Joe Mauer and his 14-game hitting streak on the bench because of a stiff back, the Twins had only two players in the lineup entering the game with a batting average better than Florimon's .247. But Trevor Plouffe doubled off the wall to start the third, and with one out Florimon drove a first-pitch curveball just inside the foul pole and just over the right-field wall to put the Twins up 2-1.
Worley's ERA was the worst in the league entering the game at 7.15, and even after this solid performance no pitcher in the majors with a qualifying amount of innings has a higher opponent batting average than his .369.
"They weren't all clean innings but he pitched out of them. A better performance by him," Gardenhire said.
Worley credited between-starts work in the bullpen to adjust his mechanics so his glove pulls toward his body instead of flying out.
"For the most part I kept the ball down, got the double play balls I needed to get," Worley said. "I'm not a strikeout guy. If I can get them to put the ball in play, I can make my defense work."
NOTES: Morneau, whose 17 RBIs are the most in the majors in May, dropped to 6 for 8 with 13 RBIs with the bases loaded this season. ... This was only the third time in nine starts with the Twins that Worley finished six innings. .. The Red Sox will send RH Ryan Dempster (2-4, 3.75 ERA) to the mound on Saturday, opposite LH Scott Diamond (3-3, 4.08 ERA) of the Twins. Both of them gave up six runs and took the loss in their last start.