Brantley put the Indians ahead with a two-run single in the sixth inning and made it 5-2 with a two-run shot in the eighth off Darren O'Day. His four RBIs tied a career high, reached twice previously.
Nick Swisher had two hits and scored a run for the Indians, and former Oriole Mark Reynolds went 1 for 2 with two walks. The victory improved Cleveland's record against the AL East to 7-17 and provided an uplifting start to an 11-game road trip.
Ubaldo Jimenez (6-4) allowed two runs in 5 1-3 innings and Vinnie Pestano, the fourth Indians reliever, worked the ninth for his fourth save.
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