Brett Lawrie hit the game's first pitch for one of Toronto's four homers and the Blue Jays tagged Jon Lester for a career-worst 11 runs in a 15-7 victory that completed a three-game sweep over the Red Sox on Sunday.
J.P. Arencibia, Rajai Davis and Travis Snider also homered for the Blue Jays.
Coming into Boston last in the division and minus one of the game's best power hitters, the Blue Jays pounded the Red Sox by a combined score of 28-11 after being swept in three games by the Yankees.
"It was just a very good offensive day and a very good weekend, considering what we came out of in New York and the loss of Jose," Toronto manager John Farrell said. "The guys bounced back and we had a very good weekend here."
Bautista who leads the club with 27 homers, is on the 15-day disabled list with a sore left wrist.
Toronto (48-47) posted a season high for runs and climbed out of the AL East cellar, moving a half-game ahead of the Red Sox (48-48). The Blue Jays matched their season high with 18 hits.
"I think the boys set the tone. First pitch of the game, Brett comes out swinging," Snider said. "J.P. and the rest of the at-bats we put together against Lester were good at-bats against a good pitcher like Lester. We've struggled (against him) before and to come out of here with a sweep is nice."
Lester (5-8) allowed a career-high four homers and nine hits. He was booed off the field after being pulled with no outs in the fifth.
"God, I hope so," said Lester when asked if he needs to get better soon. "It's getting old."
The left-hander's teammates know they need him to rebound.
"We have to have him back. Everyone goes through hard times," second baseman Dustin Pedroia said. "We're not going to turn around if Jon's not himself. We have to have him. We're not going to run away from him and turn our backs on him."
Adrian Gonzalez hit a three-run homer and Jacoby Ellsbury a solo shot for the Red Sox, who play their next six games on the road against division leaders.
Boston opens a three-game series against AL West-leading Texas on Monday and has a three-game set versus the East-leading New York Yankees next weekend.
Henderson Alvarez (6-7) pitched 5 2-3 innings, giving up seven runs and seven hits.
Lawrie belted a 95 mph fastball completely out of Fenway Park over the Green Monster. Edwin Encarnacion and Davis sandwiched RBI doubles around Arencibia's run-scoring grounder, moving Toronto ahead 4-0. Jeff Mathis then laid down a safety squeeze, scoring Davis to make it 5-0.
Gonzalez hit a three-run homer in the bottom half, but the Blue Jays scored four more runs off Lester on consecutive homers by Arencibia and Davis in the second.
Lester sounded like someone that's feeling extra pressure lately.
"It's embarrassing," Lester said. "I've let my teammates down a lot this year. It's hard for me to walk around this clubhouse and look guys in the eye right now."
Arencibia hit a three-run shot into the Monster seats after Lawrie walked leading off and Encarnacion drew a two-out walk. Five pitches later, Davis homered into the first row of seats above the left-field wall. After Lester fanned Snider for the final out, he walked slowly to the dugout to loud boos.
"We just kept on putting (good at-bats) together and to be able to score nine runs on a guy like that is tough," Arencibia said.
Gonzalez homered about 10 rows into the bleachers behind Boston's bullpen.
Mike Aviles' sacrifice fly made it 9-3 before Snider, the last batter Lester faced, hit a two-run shot onto a black tarp that covers two sections of centre-field seats during day games to help the hitters' background. Lester's ERA ballooned to 5.46 from 4.80.
In the sixth, Boston made it 11-7 on back-to-back RBI hits by Aviles and Nick Punto. Toronto added four more runs in the eighth.
The Red Sox finished a seven-game homestand 3-4 after taking three of four from the Chicago White Sox.
NOTES: Farrell said before the game that RF Bautista is "coming along better than the medical staff could have envisioned." ... Boston 3B Will Middlebrooks and LF Carl Crawford were both rested. "He's been playing a lot since the hamstring," manager Bobby Valentine said of Middlebrooks, who missed seven games earlier this month with a tight left hamstring. "Day game after a night game might be testing it. I don't want to test it." Crawford had played in every game since coming off the DL for the first time Monday, following his recovery from left wrist and elbow injuries. ... It took nearly an hour to play the first two innings. ... The Blue Jays had the leadoff batter on in the first five innings — all against Lester.