Jose Bautista and Juan Francisco also connected for the Blue Jays, who have hit a major league high 113 home runs this season.
Facing Will Smith (1-1), Jose Reyes led off the ninth with a double that left fielder Elian Herrera dove for but couldn't handle. Melky Cabrera was intentionally walked and Brandon Kintzler came on to face Anthony Gose, who failed to advance the runners with a bunt when Reyes was forced at third.
Darin Mastroianni struck out but Encarnacion ended it with a drive into the second deck in left, his 26th.
Encarnacion is tied for the major league lead with White Sox rookie Jose Abreu and Baltimore's Nelson Cruz.
Casey Janssen (3-0) worked one inning for the win.
With Bautista starting at designated hitter for the second straight game and Adam Lind at first base, Cabrera moved to right field and Encarnacion made his fourth career appearance in left. Bautista, who has been bothered by a strained left hamstring, hopes to return to the outfield Thursday.
Brewers outfielder Khris Davis was held out with a strained left shoulder. Davis, who left Tuesday's game in the seventh after he was injured sliding into second base, is expected to return Friday at Cincinnati. The Brewers are off Thursday.
Milwaukee opened the scoring with a two-out rally in the first. Jonathan Lucroy doubled down the right field line and scored on a single by Carlos Gomez.
Toronto answered in the bottom half when Bautista clubbed a two-out homer, his second in two days.
The Brewers reclaimed the lead with a three-run third, opening the inning with three straight hits. Jeff Bianchi singled and Rickie Weeks doubled before both runners scored when Ryan Braun tripled off the glove of Colby Rasmus in center. Lucroy drove in Braun with a sacrifice fly.
Adam Lind hit an RBI double in the bottom half and the Blue Jays tied it in the fourth on a two-run shot to right by Francisco, his first homer since June 20.
A botched bunt play cost the Blue Jays a chance to take the lead in the seventh. Cabrera led off the with a double and Bautista followed with his major league leading 60th walk, chasing Brewers right-hander Wily Peralta. After lefty Zach Duke came on, Toronto sent Mastroianni up to pinch hit for Lind.
But Mastroianni bunted into a double play, stumbling out of the batter's box as Cabrera was forced out at third. Encarnacion was intentionally walked but Dioner Navarro struck out.
Peralta allowed four runs and nine hits in six innings. He walked three and struck out four.
Blue Jays left-hander J.A. Happ allowed four runs and six hits in seven innings. He walked none and struck out four.
Brewers manager Ron Roenicke and Blue Jays manager John Gibbons were both ejected for arguing on separate plays in the eighth.
Roenicke was ejected for the first time this season after arguing that Toronto's Steve Tolleson had swung at a two-strike pitch that hit him in the right foot.
First base umpire Phil Cuzzi ejected Roenicke, who came out on the field to continue arguing.
One batter later, Tolleson was ruled safe as he advanced to second on a wild pitch. Bench coach Jerry Narron came out to argue and the call was overturned following review.
That brought Gibbons out for an argument with plate umpire and crew chief Greg Gibson, leading to the second ejection for Gibbons this season.
NOTES: The Blue Jays signed first round draft picks RH Jeff Hoffman and C Max Pentecost. Hoffman was selected ninth overall while Pentecost was picked 11th. ... Milwaukee is off Thursday before opening a three-game series at Cincinnati on Friday. Brewers RH Kyle Lohse (9-2) faces Reds RH Alfredo Simon (10-3). ... Toronto begins a four-game series at Oakland on Thursday. Blue Jays RH R.A. Dickey faces Athletics RH Sonny Gray (7-3).