Jeter also had a single in the first inning.
"He's meant so much to this team," Yankees manager Joe Girardi said. "You can look at so many games that he has such a big impact on... like tonight."
Even White Sox manager Ozzie Guillen was full of praise for the Yankees shortstop.
"He's the number one ambassador in this game," Guillen said.
Pettitte, who entered the game with a 3-0 record, had a rough start when Chicago belted him for three runs in the first and another in the second.
He gave up seven hits over six innings and did not figure in the decision as Alfredo Aceves (2-0), who pitched the seventh, collected the win.
The Yankees starter struggled early, allowing Paul Konerko to hit a three-run homer in the first inning for the White Sox.
"I just made a stupid pitch," Pettitte said after the ball hit the top of the right-field fence and bounced over.
(Reporting by Gene Cherry in Raleigh, North Carolina; Editing by John O'Brien)