Reliever Alex Burnett walked two batters in the eighth inning that came around to score on a game-winning bloop single from Mark Reynolds off Anthony Swarzak.
"We walked ourselves into a mess there in the end," Twins manager Ron Gardenhire said. "Walks get you every time in situations where anything can happen. And a bloop to center field ended up costing us a couple runs. So that's how you lose a ballgame at the end -- with walks."
Burnett, who entered with a 2.78 ERA, was able to get Adam Jones to pop up to open the inning, but walked Matt Wieters and Wilson Betemit to get the Twins into a jam. Chris Davis moved both runners over on a grounder to second off Tyler Robertson to set the stage for Reynolds' at-bat against Swarzak.
Reynolds was able to drop a ball in front of Denard Span in center field to bring in both runs with two outs.
"I think my bat's 34 inches, and I used all of it," Reynolds said. "It got in on me a lot. I'd been pulling off pitches all day and I was real frustrated with it."
It spoiled a strong start from rookie right-hander Cole De Vries, who bounced back after a lackluster outing against the A's on Saturday.
De Vries, who gave up a career-high seven runs in five innings against Oakland, fared much better this time around. He surrendered just one run -- coming on a solo blast from Davis in the second -- and five hits over six innings. He also struck out five and walked one.
"It was night and day just in the overall results," De Vries said. "I felt a little shaky because I didn't have my command in the first innings, but then I was able to get back to where I was before the break. I was able to locate all my pitches pretty well."
He was backed by an early lead from the Twins, who scored two runs in the first frame against left-hander Wei-Yin Chen. Josh Willingham came through with an RBI single before Trevor Plouffe added an RBI double that extended his hit streak to a career-high 17 games.
Minnesota tacked on another run in the fourth on a sacrifice fly from Alexi Casilla with the bases loaded. But the Twins left two runners on base, as Span flied out to left field to end the inning.
The Orioles scored a run in the seventh after De Vries departed, as Brian Duensing walked Davis and gave up a single to Reynolds with nobody out. Ryan Flaherty moved both runners over with a sacrifice bunt to put both runners in scoring position.
Nick Markakis then hit a grounder to third, but Plouffe's throw to home sailed high, allowing Davis to score, Reynolds to reach third and Markakis to advance to second. The Twins decided to walk J.J. Hardy to get to Jim Thome with the bases loaded and the moved paid off, as Thome grounded into an inning-ending double play.
The Twins saw a late rally in the eighth fall short, as Willingham and Justin Morneau reached base with nobody out but failed to score. Plouffe popped out before Darin Mastroianni, who entered as a defensive replacement in the eighth, grounded out and Brian Dozier flied out to center.
It forced Minnesota to settle for a split in the four-game set despite winning the first two games of the series.
"The way they thumped us around, they were really swinging the bats well the first two games," Orioles manager Buck Showalter said. "That's a pretty tough lineup to go through. It's frustrating, cause we had some chances to really open it up some, with a lot of runners out there. It's kind of crazy how the game is, because it kind of revolves around a flare that Mark threw out there in center field."