Emilio Bonifacio went 3-for-4 with three runs scored and a two-run blast while Edwin Encarnacion contributed three hits, a solo shot and two RBI for the Blue Jays, who took the rubber match of a three-game series.
Brent Lawrie also went deep and Munenori Kawasaki chipped in with two RBI for Toronto.
Chad Jenkins (1-0) earned the victory in his first appearance after starting the season on the disabled list. The right-hander allowed two runs on seven hits over five innings, yielding one walk while fanning two.
Red Sox starter Ryan Dempster (2-4) was roughed up for six runs on seven hits in a five-inning effort.
Mike Napoli went 3-for-4 with a solo homer and Pedro Ciriaco also hit one out for Boston.