"We were kidding [Cabrera] before the game, asking him if he was going to hit one and he hit two," Tigers manager Jim Leyland said.
Zach Miner allowed one run and six hits in 5 2/3 innings for Detroit, which lost its first seven games last year and finished last in the AL Central.
The Tigers were beaten 12-5 on Opening Day this year and absorbed a difficult 5-4 loss Tuesday in a game they led 3-0 through seven innings.
Cabrera made sure the slump would not continue, hitting a three-run drive in the first and a solo shot in the fifth that bounced off the center-field restaurant at Rogers Centre.
"It was kind of neat," Leyland said of Cabrera's fifth-inning drive. "There was a [fan] out in center field that looked like he was getting ready to catch it. All of a sudden he turned his head and looked up. You don't see many like that."
Cabrera added a single in the eighth and finished 3-for-4. He is 7-for-10 with two walks this season.
Cabrera led the AL with 37 homers last season but Leyland expects him to do even better this year.
"He came over here last year and there was a lot of pressure on him," Leyland said. "He was with a new team, it took him time to settle in. Once he did, you saw what happened. Now he's off to a great start. He's a great player, he's much more comfortable. I know he likes it here, he's settled in more. There's no telling what he can do. He's that good."
Learning how AL pitchers try to handle him has made life easier on Cabrera.
"I had to learn the league, you know," he said. "I had to make a lot of adjustments. Right now I feel more comfortable because I know the league better, I know how they're going to pitch me. I feel more relaxed. I'm not thinking a lot at home plate, I make my adjustments and that's it."
Inge added a solo shot in the sixth for the Tigers, who have six homers in three games. Inge is the first Tiger in more than 50 years to homer in the first three games of the season.
"It's an honor, a big honor," he said.
Bobby Seay followed Miner (1-0) with 1 1/3 innings, Ryan Perry tossed a perfect eighth in his major league debut and Fernando Rodney finished for Detroit. Curtis Granderson crashed into the wall in center to snare Lyle Overbay's drive for the final out.
"When he hits the ball, usually they're asking for a new ball," Miner said.
The Blue Jays got one back in the bottom half when Marco Scutaro and Aaron Hill hit back-to-back doubles. Alex Rios followed with a single and Vernon Wells walked to load the bases for Adam Lind, but Toronto couldn't sustain the rally. Hill was forced out at the plate on Lind's grounder and Rios was thrown out at home by Josh Anderson on Scott Rolen's fly to shallow right.
"Sometimes the biggest play of the game is in the first inning or the second inning, it's not just in the ninth inning, the last out of the game," Leyland said. "That was probably the biggest play of the game, as it turned out."
Litsch (0-1) surrendered five runs and seven hits in six innings for Toronto.
Thursday's series finale will mark the first time since baseball's draft began in 1965 that two first-round picks will face each other in their respective major league debuts. Toronto will start left-hander Ricky Romero, the sixth-overall pick in 2005, while Detroit counters with right-hander Rick Porcello, taken 27th in 2007. ... Wednesday's loss denied the Blue Jays the third 3-0 start in club history. Toronto started 3-0 in 1992 and 1996.