Jacoby Ellsbury led off the game with a home run and Adrian Gonzalez hit an RBI triple as the Red Sox roughed up Freddy Garcia (4-5) early to move within two percentage points of the first-place Yankees in the AL East.
New York first baseman Mark Teixeira left the game in pain after getting hit on the kneecap by a first-inning pitch from Jon Lester.
Derek Jeter had two hits to move within 12 of 3,000. He entered the 10-game homestand with 2,986 and said the most pressure he feels in his march toward the milestone is reaching the mark at Yankee Stadium.
Working on seven days' rest, Lester (8-2) gave up three runs and eight hits — seven singles — in six innings.
The Red Sox have been on a tear since arriving in the Bronx on May 13, starting a run in which they have won 17 of 23 with a three-game sweep of the Yankees. They have beaten New York in six of their seven meetings this year.
Papelbon, pitching while he appeals a three-game ban for making contact with an umpire Saturday, gave up an RBI single to Jorge Posada but struck out Alex Rodriguez with a runner on second for his 12th save. He reached 200 saves in 359 appearances, fewest in baseball history. Mariano Rivera is next at 382 games.
Red Sox reliever Bobby Jenks left in the seventh after throwing just four pitches because of tightness in his back. Matt Albers came on and finished a walk to Posada before retiring three in a row. Daniel Bard was perfect in the eighth.
Ellsbury hit the fourth leadoff homer of his career, and the Red Sox chased Garcia soon after.
Garcia, along with Bartolo Colon, has been a steady surprise for the Yankees, helping to fill voids in the rotation left by the retired Andy Pettitte and injured Phil Hughes.
Garcia had gone at least five innings in each of his nine starts this season, but was knocked out after just 1 2/3 innings.
After Ellsbury connected, Dustin Pedroia walked, Gonzalez tripled and Kevin Youkilis hit a sacrifice fly.
Pedroia had an RBI double in the second to make it 4-1. Garcia intentionally walked Gonzalez to load the bases, ending his night.
Restless Yankees fans booed as Garcia walked off the field having given up four hits, three walks and four runs.
The Yankees scored in the bottom of the first, taking advantage of Lester's early wildness, but received a scare when Teixeira was hit On the right knee by a pitch from Lester. Teixeira immediately crumbled to the dirt and rolled back and forth, holding his knee.
He had trouble putting weight on his leg and was assisted off the field. X-rays were negative and Teixeira will be re-evaluated Wednesday.
Posada, on the bench with the left-handed Lester on the mound, ran for Teixeira and stayed in at first base.
Robinson Cano drove in Curtis Granderson, who walked. Lester also hit Russell Martin with a pitch near the right knee, but Martin walked to first and appeared to be unhurt.
Posada, who pulled himself out of the lineup after he was dropped to ninth in the order the last time the Red Sox were in town, later got his first two hits of the season against a lefty. He snapped an 0-for-27 skid from the right side with a single in the third inning.
Ortiz hit a two-run shot off Hector Noesi in the fifth to make it 6-1.
Nick Swisher had a two-run double in the bottom half.
Notes
To make room for Marco Scutaro, who was activated from the DL, the Red Sox sent RHP Scott Atchison to Triple-A Pawtucket. … RHP Phil Hughes (shoulder inflammation) threw off a mound at the Yankees' complex in Tampa, Fla., and is expected to throw a simulated game Thursday. … RHP Carlos Silva was put on the DL at Triple-A Scranton/Wilkes-Barre because of shoulder stiffness. Silva was released by the Chicago Cubs during spring training and agreed to a minor league contract with New York on April 9. … Jeter introduced the DJ3K bracelet marking his pursuit of 3,000 hits. Proceeds from the sale of the silicone bracelets will benefit his Turn 2 Foundation.