Jed Lowrie hit a three-run homer off Pettitte and went 4-for-4, setting a career high for hits. Bill Hall added a three-run shot against Jonathan Albaladejo, handing Red Sox starter Josh Beckett a 10-1 cushion in the fifth.
Alex Rodriguez rallied the Yankees with a pair of home runs, giving him 610 to pass Sammy Sosa for sixth place on the career list. Mark Teixeira also connected twice as New York went deep a season-high six times, yet fell a half-game behind Tampa Bay with its third straight defeat. The Rays beat Seattle 5-3.
Teixeira hit a solo shot and Rodriguez walked with two outs in the ninth before Jonathan Papelbon struck out MVP contender Robinson Cano to end it.
Teixeira, Rodriguez, Curtis Granderson and Nick Swisher all homered off Beckett, who entered 0-2 with an 11.17 ERA in four starts against the Yankees this year.
Rodriguez's second homer, off reliever Scott Atchison, cut it to 10-7 in the seventh and got the sellout crowd of 49,457 buzzing. But the Red Sox bullpen closed it out, with Daniel Bard tossing a scoreless eighth and Papelbon earning his 37th save in 44 attempts.
Marco Scutaro ended Pettitte's night with a two-run single that capped a four-run fourth, sending Boston to its fifth consecutive victory on the road. The Red Sox are 6 1/2 games behind New York in the wild-card race with nine to play.
The Yankees came into the series opener knowing they could clinch their 15th playoff berth in 16 years by beating their biggest rivals twice in the three-game set.
But the injury-riddled Red Sox, who have five games remaining against the Yankees, could still make some noise – and give New York a huge scare – if they go on a late tear.
Rookie right-hander Ivan Nova and spot starter Dustin Moseley are slated to pitch the final two games of the series for New York. Jon Lester and Daisuke Matsuzaka get the ball for Boston.
J.D. Drew had three hits for the Red Sox, and Mike Lowell scored three times before leaving the game after getting hit in the face by a bad-hop grounder. Lowrie also scored three times.
In his second outing since missing two months with a strained left groin, Pettitte (11-3) fell behind several hitters and had trouble putting others away. He gave up seven runs – six earned – and a season-high 10 hits in 3 1/3 innings.
He lasted only 75 pitches, not what the defending World Series champions had in mind as they try to get him stretched out for October. The left-hander came off the DL on Sunday in Baltimore and had an encouraging start, yielding one run and three hits in six innings.
Beckett (6-5) went 6 2/3 innings, giving up five runs and seven hits.
Notes
Lowell was hit in the face by Granderson's bad-hop single to first in the fifth. He crumpled to the ground as manager Terry Francona and a trainer rushed out of the dugout, but the 2007 World Series MVP received a warm ovation as he rose to his feet and remained in the game – temporarily. He was replaced by Lars Anderson in the sixth. … The four home runs served up by Beckett were a season high. … Derek Jeter extended his season-best hitting streak to 13 games.