Encarnacion's two-run shot off Sean O'Sullivan in the first inning went over batter's eye screen in center field. It was the first of the spring for Encarnacion, who has struggled to a .118 average. He also previously missed 16 games with back inflammation.
Bautista's drive in the fifth, also against O'Sullivan, landed far over the left field fence. Donaldson followed up two batters later with a solo drive off reliever Luis Garcia that easily cleared the 400-foot mark in center.
Prospect Rowdy Tellez added a two-run shot to right for Toronto in the eighth.
O'Sullivan, a candidate for the fifth spot in Philadelphia's rotation, allowed five hits and five runs in four innings. He also walked four and struck out two.
Toronto starter Aaron Sanchez was roughed up in 4 1-3 innings. The right-hander gave up four runs on six hits with six walks and two strikeouts.
''He's going to have some outings like that,'' Blue Jays manager John Gibbons said. ''He's got that good, live fastball and sometimes it gets away from him. That's part of it. . Today was just a bad day for him. I still think he's going to have a big year for us.''
Grady Sizemore drove in a run for the Phillies.
HUTCHISON GETS OPENING-DAY NOD
Phillies: O'Sullivan said he wasn't aware he was starting until his wife saw a post about it on the Internet Monday night. The righty hadn't pitched in five days after being hit on his throwing hand with a comebacker in a minor league game.
''I was like, `I'm not going to believe anything until someone tells me what's happening,''' O'Sullivan said. ''So, I showed up this morning and they were like, `Hey you're over there (starting) today.' ... But that kind of thing shouldn't be a factor.''
Blue Jays: Toronto picked Drew Hutchison to make his first opening-day start, and the right-hander is slated to face the Yankees and Masahiro Tanaka on April 6 in New York.
At 24 years old, Hutchison will be the youngest opening-day starter in franchise history. He is 1-2 with a 4.80 ERA in three career starts at Yankee Stadium.
After missing the 2013 season while recovering from elbow ligament-replacement surgery, Hutchison was 11-13 with a 4.48 ERA in 32 starts last season. He is 3-0 with a 1.80 ERA in four spring training appearances.
R.A. Dickey had started Toronto's previous two openers.
Phillies: RHP Ken Giles was removed from the game with one out in the eighth as a precaution after feeling tightness in his lower back. Giles said he doesn't believe it's serious and should be ready for opening day. ... General manager Ruben Amaro said OF Domonic Brown, who has been sidelined since leaving a March 19 game against the Yankees with left achilles tendinitis, will be on the disabled list to start the season.
Toronto rookies Dalton Pompey and Devon Travis could hardly contain their excitement after both were informed they had made the team. Pompey, a Toronto native, will start in center field, and Travis, acquired in an offseason trade with Detroit for Anthony Gose, won the second base job.
''My mouth, my heart - everything dropped,'' said Travis, who has never played above Double-A ball. ''It's something that I've dreamed of forever. So, when you get that news, it's kind of hard to all grasp at one time. In these next 24 hours, hopefully it will sink in and I can enjoy it.''
Pompey earned September callup with the club last season, but said playing on opening day will be a lifelong memory.
''It's kind of like a deep breath,'' he said. ''I can kind of relax a little bit and move forward and get ready for the season and know that I'm going to be there.''
Phillies: RHP Kevin Slowey was released. Slowey, who went 2-1 with a 6.94 ERA in seven exhibition appearances, was in the mix for the fifth spot in the rotation.
Blue Jays: OF Dayan Viciedo was granted a release from his minor league contract after being told he would not make the opening-day roster. ... LHP Jeff Francis, OF Caleb Gindl and INFs Jonathan Diaz and Munenori Kawasaki were reassigned to minor league camp. C Josh Thole was optioned to Triple-A Buffalo.
Phillies: Cole Hamels will make his final exhibition start on Wednesday against the Braves in Clearwater.
Blue Jays: Toronto will conclude its Grapefruit League schedule on Wednesday against the Red Sox in Fort Myers, before traveling to Montreal for two games against Cincinnati on Friday and Saturday at Olympic Stadium.