Marco Scutaro finished 4-for-5 with three 0, in the second edition of a four-game series.
David Ortiz collected four hits and knocked in two, Adrian Gonzalez posted three hits and drove in two runs, while Jarrod Saltalamacchia hit a two-run homer for the Red Sox, who recovered from a 1-0 loss in 11 innings in Monday's series opener and won for the second time in their last six games. Boston had 20 hits, including nine doubles.
Lester (15-6) posted his fourth straight positive decision, tying a season-high of 11 strikeouts while allowing just three hits and one walk.
The wild card-leading Red Sox remained 2 1/2 games behind the first-place Yankees in the AL East.
"We kept at them, spread it out and Lester threw a bunch of strikes," Boston manager Terry Francona said.
Luis Perez (3-3) was tagged for 10 hits and eight runs over 2 2/3 innings for the Blue Jays, who have dropped four of five.
The Red Sox gave Lester all the runs he needed in the first, tallying four times on RBI singles from Ortiz and Scutaro bookended by RBI doubles from Gonzalez and Carl Crawford.
Scutaro led off the third with a double and scored on Saltalamacchia's one- out, two-run homer. Darnell McDonald singled and Ellsbury grounded out, but a Dustin Pedroia reached safely on an error from Brett Lawrie. Perez exited for Rommie Lewis, who prevented further damage by fanning Gonzalez.
Boston went ahead 11-0 in the fourth on consecutive run-scoring doubles by Ortiz and Scutaro and a single from McDonald.
The visitors then welcomed reliever Dustin McGowan back to the majors for his first appearance since July of 2008 with Scutaro's two-run double in the fifth. Gonzalez, who singled, and Ortiz, who reached on a double, scored on the play.
"When guys are struggling I can tell them it's not the end," McGowan said. "Some things you have to battle through and hope it will work out."
Josh Reddick lined a solo homer off the top of the wall in right in the eighth to cap the outburst of runs.
Kyle Weiland turned in two scoreless relief frames to close out the rout.
Lester also fanned 11 on May 3 against the Angels...Boston's nine doubles were the most in one game since July 21, 2003 against Detroit...Toronto starter Ricky Romero was named the AL pitcher of the month for August on Tuesday, the first Jays hurler to earn the honor since Roy Halladay in April, 2007...Prior to the game, the Red Sox officially confirmed the diagnosis of a sprained right ankle for starter Josh Beckett, who will miss his scheduled turn in the rotation this weekend...McGowan was charged with three runs on five hits with five strikeouts and three walks in four-plus frames.