Minnesota was able to chase New York starter Phil Hughes in the deciding seventh inning after a pair of singles and a walk loaded the bases with two outs. Yankee reliever Boone Logan came on to work out of the jam but promptly allowed four runs to score.
Minnesota centerfielder Denard Span had the big blow in the seventh with a two-run double followed two batters later by a run-scoring single off of the bat of catcher Joe Mauer.
Casey Fien (2-1) earned the win in relief while Glen Perkins picked up his 15th save of the season despite giving up a home run to Andruw Jones in the ninth inning.
The Yankees scored all of their runs via the long ball. In addition to Jones' last-gasp blast, Nick Swisher hit a two-run homer in the fourth inning followed later by a solo shot from Russell Martin in the top of the seventh.
The loss kept the Yankees two games ahead of the Baltimore Orioles in the AL East race. The Twins have now won three of their last four games as the two teams finish the series on Wednesday afternoon at 1:10 p.m. ET.