Donaldson's drive into the second deck of the left-field stands was his third hit of the afternoon. He hit 29 homers last year with Oakland, was traded to Toronto in the offseason and launched his first two home runs Friday night in an 8-7 loss.
Donaldson connected on the second pitch from Sugar Ray Marimon (0-1), handing Atlanta its first road defeat of the season.
Toronto reliever Brett Cecil (1-1) picked up the win after working a scoreless 10th.
Down 4-0 in the seventh inning after home runs by Freddie Freeman and A.J. Pierzynski, the Blue Jays rallied against Alex Wood with the help of Jose Bautista's third homer.
Atlanta's Kelly Johnson hit a solo home run in the ninth that made it 5-all.