Edwin Encarnacion added a two-run blast while Yunel Escobar supplied a two-run double as the Blue Jays improved to 3-3 on a nine-game homestand.
Kyle Drabek (2-0) earned the win, surrendering only one earned run on six hits over 7 1/3 innings. The right-hander struck out six and issued only one walk in the performance.
Orioles starter Brian Matusz (0-2) was touched for five runs on seven hits in 5 2/3 frames, walking four and striking out four.
Adam Jones homered and Ronny Paulino added an RBI for Baltimore.