Encarnacion's two-run blast in the second inning handed the Blue Jays a 4-0 lead and his two-run double in the next frame capped a five-run outburst that broke the contest open.
J.P. Arencibia went 3-for-4 with a run batted in while Maicer Izturis and Emilio Bonifacio each provided two hits and an RBI for the red-hot Blue Jays, who completed a three-game sweep of the Orioles and moved two games above .500 (38-36).
Josh Johnson (1-2) earned his first win of the season, yielding four runs on seven hits over six innings. He walked one and struck out five.
O's starter Freddy Garcia (3-5) lasted just 2 1/3 frames after being lit up for seven runs on seven hits.
Ryan Flaherty pounded a pair of homers in Baltimore's loss.