Colby Rasmus hit a three-run homer and J.A. Happ pitched scoreless ball into the sixth as Toronto downed Boston, 5-0, in the middle test of a three-game set from Rogers Centre.
J.P. Arencibia added a two-run blast for the Blue Jays, who shook off a 6-4 loss in Friday's series opener and won without the services of outfielder Jose Bautista, shelved for the second straight game with a sore right ankle.
Happ (1-0) allowed just one hit and three walks with six strikeouts over 5 1/3 innings.
"Happ was just dynamite," Blue Jays manager John Gibbons said."He started throwing his changeup more and that was a big pitch for him."
Jacoby Ellsbury and Dustin Pedroia were the only players to record a hit for the Red Sox, who were blanked for the first time in 2013.
John Lackey (0-1) made his first start since the end of 2011 due to Tommy John surgery, but lasted only 4 1/3 innings before leaving with what was diagnosed as a right bicep strain. The 34-year-old exited after serving up five hits and two runs with eight strikeouts and one walk.
"After going a year and a half of getting to this point and having to do it all over again, yeah, it scared the crap out of me," said Lackey. "But it was a serious cramp. It's not the elbow. It's sore but we're hoping its not serious."
Arencibia's blast to dead center put the Jays on the board with one down in the fourth. Adam Lind, who singled in the prior at bat, also came in on the homer.
Lackey left the game after working the count to 3-2 on Toronto shortstop Jose Reyes. He walked off the mound dangling his right arm by his side and holding the area around his elbow.
Alfredo Aceves took the hill, but the hosts piled on.
Toronto took a 5-0 lead in the sixth when Lind worked a leadoff walk, Mark DeRosa walked with two down and Rasmus drove a pitch over the wall in right center.
"I've hit a few pretty far, but I hit that one pretty good," said Rasmus.
Boston went quietly in the seventh and eighth, then Pedroia's two out single was the lone blip for Sergio Santos in the ninth.
Toronto last blanked an opponent on Sept. 27, 2012, a 6-0 win over the Yankees at home ... Lackey went 12-12 with a 6.41 ERA in 28 starts for Boston two years ago ... Shane Victorino and Pedro Ciriaco also reached for the Sox via walks...The Blue Jays were the last team to blank the Red Sox, in a 5-0 decision on Sept. 16, 2012 ... Prior to the contest, the Jays selected the contract of pitcher Dave Bush from Triple-A Buffalo and designated pitcher Jeremy Jeffress for ssignment.