Cano belted a two-run shot in the third inning, putting the Yanks up 3-0, and added another with a man aboard in the fifth for a 5-1 advantage.
Travis Hafner also hit a two-run home run for New York, which clinched its three-game series.
Yankees' starter David Phelps (2-2), making his fourth start while filling in for the injured Ivan Nova, went seven innings, allowing one run on six hits while walking three and striking out eight.
Blue Jays starter Brandon Morrow (1-3) yielded five runs on seven hits over five frames.
Edwin Encarnacion went deep for Toronto.