Nick Swisher, Eric Chavez and Bobby Crosby each drove in runs to help Chad Gaudin to his fifth straight win.
Santana, who had won his last two starts, struck out four but also walked a season-high four batters and ran into trouble right away in the first, then again in the third. He allowed four runs, three of them earned, and five hits in six innings.
Jason Kubel homered for Minnesota to start the sixth, snapping a 67-inning homerless streak for Gaudin. Michael Cuddyer knocked in Minnesota's first run with an R-B-I single in the fifth.