The Red Sox trailed by a run heading into the sixth, but scored eight times over the final four innings while rolling to their fifth straight victory.
Cody Ross drove in the first run of the inning with a single and, after Kelly Shoppach fanned for the second out of the inning, McDonald cleared the bases with a double to left. McDonald scored on a single by Marlon Byrd.
Ross also had an RBI single during a two-run seventh and McDonald tacked on a solo homer in the ninth, his first of the season.
McDonald had compiled just 30 at-bats this year prior to Friday and was batting a mere .100.
Starter Daniel Bard was credited with the win after allowing three runs on six hits in six innings. frames. During their five straight wins the Red Sox have outscored the opposition 44-19.
Chicago has lost four in a row.