Middlebrooks hit his third career grand slam and a three-run homer. The Red Sox, who clinched the AL East title last week, moved two games ahead of Oakland for the best record in the league and home-field advantage throughout the postseason.
David Ortiz hit a two-run double to reach 100 RBIs this season. Jacoby Ellsbury didn't take long to energize the Red Sox lineup as he returned after missing 16 games with a fractured right foot — he singled, walked and scored twice before being replaced in the fourth.
Jake Peavy (12-5) earned his first win since Aug. 31, allowing five runs and eight hits in six innings.
Jhoulys Chacin (14-10) gave up seven runs and nine hits in four innings, tying his shortest outing of the season.