Lowrie crushed a Casey Janssen (4-2) offering into the bullpen in right field, giving the Sox a measure of revenge for being on the wrong end of a 16-2 blowout loss Friday in the series opener.
The hit made a winner of Jonathan Papelbon (5-5), who turned in a scoreless top of the frame.
Victor Martinez finished 3-for-5 and drove in three runs for the Red Sox, who stopped a two-game slide. Daisuke Matsuzaka started and allowed six hits and four runs with eight strikeouts and three walks over eight innings.
Ricky Romero got the nod for Toronto and gave up nine hits and four runs while fanning eight over seven full frames.
The Sox picked up two runs in the third. Darnell McDonald walked with one out and Marco Scutaro followed with a double, then after J.D. Drew was hit by a pitch Martinez knocked in a pair with a base hit.
John McDonald's RBI double with two down in the fourth got the Jays on the board, but a tying run in Overbay was thrown out at the plate to end the frame.
Boston added two more runs in the fifth with run-scoring hits by Martinez and Adrian Beltre, but Toronto countered with three in the sixth on a Buck sacrifice fly and a two-run shot from Overbay.
Although they had runners on first and second with one out in the eighth, the Red Sox failed to score after Darnell McDonald fanned and Scutaro grounded into a fielder's choice.
The home team also failed to get a runner home from first in the ninth.
Boston has won 10 of the 14 meetings with Toronto this season, and three of five at Fenway...Red Sox DH David Ortiz saw his 11-game hit streak come to an end...Scutaro ended with three hits and Drew notched a pair.