Napoli finished with five RBIs and scored twice for the Red Sox, who rebounded from Sunday's doubleheader sweep against the Kansas City Royals for their seventh win in nine games. Felix Doubront (2-0) matched a career high with five walks while allowing three runs and three hits over 6 2/3 innings.
A.J. Griffin (2-1) endured his worst outing in 19 career starts, surrendering a career-high nine runs (seven earned) and eight hits over four innings.
Oakland jumped out to a 2-0 lead in the second inning when Jed Lowrie scored on a wild pitch and Josh Reddick followed with an RBI single. Napoli countered with a run-scoring double in the bottom half and Middlebrooks gave Boston the lead for good with his line-drive homer that easily cleared the Green Monster.
Leading 4-3 in the fifth, the Red Sox took control when a fielding error helped load the bases for Napoli, who crushed Griffin's low fastball over the wall in left-center. Oakland halved its deficit with three runs in the eighth, but Junichi Tazawa pitched out of a jam and Andrew Bailey posted his fourth save.
NOTEBOOK: Napoli's slam was the first by a Sox hitter since David Ortiz hit one against the Marlins on June 20, 2012. ... Oakland lost for the first time in Griffin's last eight starts, including the postseason. ... The Athletics scored two more runs Monday than they did while dropping all three games against the Tampa Bay Rays over the weekend.