The win completes the sweep over Boston (91-67), something the Jays have not done at Fenway Park since June of 2001.
They have hit an impressive 35 home runs in the month of September.
Roy Halladay (17-10) started for the Jays, his last of the season, and had a no-hitter until the sixth inning when Joey Gathright singled on a line drive to Travis Snider.
Halladay threw a complete game, three-hit shutout in what may be his final appearance in the Toronto uniform.
Tim Wakefield (11-5) only pitched three innings for the Red Sox and gave up five earned runs in the loss.
The Jays had lost six straight to the Red Sox before Monday and were outscored 40-18 over that stretch.
On Tuesday night, Toronto designated hitter Adam Lind was hit in the elbow by a pitch from Jonathan Papelbon in the ninth inning, after Lind had belted three home runs earlier in the game.
He did not play on Wednesday as a result.
Boston designated hitter David Ortiz led off the bottom of the second and was hit in the elbow from Halladay’s first pitch, one that almost went behind the Red Sox slugger.
Halladay received a warning, but nothing else came of the altercation.
With the Jays leading 2-0 in the top of the third, Toronto produced back-to-back home runs, a two-run blast from Overbay and a solo-shot from Ruiz to give them a 5-0 lead.
Ruiz hit his second homer, in the sixth, to make it 9-0 for Toronto. Two batters later, McDonald drove in his second run of the game and the Jays’ tenth.
Bautista smashed a homer into the Fenway parking lot in the eighth to put the Jays up 11-0. He drove home three runs on Wednesday.
Overbay gave the Jays a 12-0 lead in the ninth with an RBI groundout.
Hill finished the game with three hits and two RBIs in six at bats. He has now driven in 107 runs this season, good enough to place him fifth in the American League.