Ryan Doumit finished with two hits, including a solo homer, and scored twice as Minnesota used a late charge to down Boston, 6-1, in the second edition of a four-game series.
Joe Mauer added two hits and an RBI, with Justin Morneau, Trevor Plouffe and Wilkin Ramirez driving in a run each for the Twins, who dropped a 6-5 decision in 11 innings in Monday's opener and won for the third time in their last eight.
Scott Diamond (3-2) worked seven scoreless innings, giving up three hits and striking out two without issuing a walk.
"I was able to work down for the most part and keep guys back off the plate so I could expand (the zone) away," Diamond said.
Jarrod Saltalamacchia's ninth-inning homer stood as the lone offense for the Red Sox, who have lost four of their last five.
Ryan Dempster (2-3) allowed five hits and four runs -- two earned -- with eight strikeouts over his seven-plus frames.
"Very good outing by Ryan Dempster," Red Sox manager John Farrell said of his starter. "Unfortunately not much to show for it on our end."
The Twins broke open a two-run game in their second-to-last turn at the plate.
Sox shortstop Pedro Ciriaco couldn't corral a Brian Dozier grounder, then failed to grab one from Jamey Carroll, and after Dempster was spelled by Craig Breslow, Mauer followed with an RBI double. Josh Willingham walked to load the bases, and Morneau plated Carroll with a single. Plouffe added another RBI hit and Alex Wilson came on, and when Willingham was out at home on Doumit's fielders' choice grounder, Saltalamacchia's wild throw allowed Morneau to cross the plate.
Boston's backstop greeted Josh Roenick with a leadoff shot to left, but that was all the hosts had in the tank.
Doumit began the fifth with a double, moved up on a Dempster balk, then scored on a Ramirez single.
It was 2-0 in the seventh on Doumit's one-out solo homer.
Red Sox DH David Ortiz extended his career-best hitting streak to 27 straight games dating back to July 2, 2012, thanks to a 1-for-4 performance ... It is the longest active streak in the majors and the longest hit streak by a BoSox player since Manny Ramirez also hit safely in 27 straight from July 15-Aug. 12, 2006 ... Prior to the game, the Sox placed closer Joel Hanrahan on the 15- day DL and recalled pitcher Allen Webster from Triple-A Pawtucket.