Trailing 4-3 entering the eighth, the Red Sox erupted for four runs and went on to notch a second straight win over Cleveland.
Pedro Ciriaco (3-for-4) ignited the rally with a one-out double against Vinnie Pestano (1-1) and scored the tying run when the next batter, pinch-hitter Mike Carp, smacked a two-base hit off the left-field wall.
Pedroia followed with a shot that just missed clearing "the Green Monster" at rainy Fenway Park, settling instead for a decisive RBI double.
Daniel Nava added a two-run bloop single later in the frame as Boston improved to 8-3 in its last 11 games.
Junichi Tazawa (4-2) earned the decision with a scoreless eighth and Andrew Bailey collected his sixth save for the Red Sox.