Jose Bautista hit a two-run homer in the ninth off Jonathan Papelbon. Then a single by Encarnacion and a walk to J.P. Arencibia put runners at first and second with two outs. John McDonald looped a single that Darnell McDonald charged and, on the run, fired the ball on the fly to Jason Varitek.
The catcher blocked home plate with his left leg and tagged Encarnacion to end the game.
Papelbon got his 18th save in 19 chances while Matt Albers (3-3) picked up the win.
Brett Cecil (1-4) went all the way for Toronto.