The Orioles scored three times in each of the first three innings, came up with four home runs overall and then held on while the Blue Jays were pounding out 17 hits.
Baltimore has won three out of four.
The Orioles had 16 hits of their own, three of them coming from Manny Machado. He became the first Baltimore player in history to record at least three hits in five straight road games.
Adam Jones tacked on a solo shot in the sixth to give the Orioles a 10-5 lead.
Chris Tillman (4-2) benefited from the home run onslaught to get the win, giving up three runs on 10 hits with seven strikeouts in five innings.
Toronto's Sean Nolin (0-1) made his major league debut and it lasted only 1 1/3 innings. He surrendered six runs on seven hits.