Jeter broke a 1-1 tie in the top of the eighth with a three-run homer deep to left field off Boston starter Curt Schilling (8-8).
Mariano Rivera battled in the bottom of the ninth, as the hometown Red Sox scored a run and loaded the bases with two outs, before David Ortiz popped out to Jeter to end the game and give Rivera his 28th save of the season.
Joba Chamberlin (2-0) was the winning pitcher in relief of Roger Clemens, who departed after giving up one run on two hits in six innings.
Schilling gave up six hits and four runs in 7 2/3 innings and struck out two.
Mike Lowell had two RBI for the Red Sox, including a solo home run in the eighth -- his 19th homer of the year -- to make it 4-2. Lowell led off the scoring in the first when his base-hit off Clemens brought in Jacoby Ellsbury, to the delight of the 36,533 at Fenway Park.
The Yankees tied the game 1-1 in the fifth on Robinson Cano’s 18th home run.