New York came into the fifth inning with a 2-1 deficit but scored four times and went on to take the rubber match of a three-game set with the Blue Jays.
Jorge Posada doubled to lead off the frame and Brett Gardner and Francisco Cervelli followed with singles to tie the game. One out later, Granderson lined a 3-2 pitch into the right field stands, putting the Yanks in front to stay.
Ivan Nova (2-2) earned the win, allowing two runs on six hits over six frames. Three Yankees relievers combined for 1 2/3 scoreless innings and Mariano Rivera collected his 10th save with a 1-2-3 ninth.
Jesse Litsch (2-2) was tagged with the loss, surrendering five runs on six hits over six innings.
Adam Lind launched a solo homer among his two hits for the Blue Jays.