"Derek is a winner and he's used to winning," Yankees manager Joe Girardi said. "He doesn't accept losing very well. Derek would trade everything for a win."
With five games to spare in the Stadium's final homestand, Jeter had his big moment in the first inning, drilling the first pitch he saw from Floyd through the legs of third baseman Juan Uribe.
Jeter received a loud ovation as the ball skidded into left field, but official scorer Bill Shannon needed to give the play a second look.
In the press box, Shannon announced, "Base hit," and the Yankees' second hit clicked onto the digital scoreboard in left-center field, drawing another roar from a sellout crowd of 52,558 as they saluted Jeter.
Most of the Yankees' roster moved to the top step of the dugout to applaud Jeter, and standing at first base, the shortstop doffed his batting helmet to a loud ovation as his image was displayed on the video screen in right-center field.
"There's so much history here at Yankee Stadium that to be a part of it is something special," Jeter said. "I think this whole last week will be pretty special here."
Jeter would finish the evening with two hits to give him 1,271 in the Bronx, a record that can never be broken. But it was to be the high point of the night for the Yankees, who went 2-for-12 with runners in scoring position and left Pettitte with his career-high fifth straight loss.
Pettitte (13-14) has already been given the honor of pitching the final game at Yankee Stadium on Sunday, so this was to be his final tuneup before that memorable occasion.
On a homestand where he had already witnessed longtime teammate Mariano Rivera pass Lee Smith for second place all-time in saves and now Jeter's accomplishment, the left-hander might have hoped for better results, working six innings and allowing four runs on six hits.
"It's wonderful to watch them do what they're doing," Pettitte said. "It's kind of sick to watch me doing what I'm doing right now. But it's great to see those guys do what they're doing, that's for sure."
Pettitte walked three -- one intentionally -- and struck out four as he left trailing, ensuring he will head to the mound against the Orioles on the Stadium's final day searching for an elusive victory. Perennially a strong second-half pitcher, Pettitte has only one win since July 31.
"I'm so disappointed with the way this stretch has gone for me that I am so excited to be pitching that last game here," Pettitte said. "I'm thankful that they've lined me up to get it. I hope I can go out and give us a good outing and get us a win in that game."
Alexei Ramirez slugged a solo home run, his 18th, leading off the third, and Pettitte ran into more trouble in the fourth as he got up in the strike zone and the White Sox batted around to add three runs.
The damage in that frame came on run-scoring hits by Ken Griffey Jr. and Paul Konerko, plus a bases-loaded walk to Juan Uribe that forced in Chicago's fourth run.
"It's unfortunate, because I thought he threw the ball pretty well," Girardi said. "He seemed to get up in the zone a little bit, and then he got right back down and settled in again.
"I know this is killing him. He's giving us everything he's got."
The Yankees (80-71) struck starter Gavin Floyd for runs in the third and fourth innings. Brett Gardner singled to open the third, stole second and scored when Johnny Damon's double fell into right-center field, and Jason Giambi cracked his 31st home run to lead off the fourth.
In a twist, some of Jeter's actions set up innings where the Yankees could have scored, but didn't. The first-inning hit off Floyd gave New York two on with none out, but Floyd (16-7) ensured it came away empty-handed. Jeter sacrificed Damon to third base with one out in the third, but Bobby Abreu grounded back to the mound and Alex Rodriguez flew out.
Jeter was also on board as New York loaded the bases in the fifth, but Giambi worked a 12-pitch at-bat before striking out to end the inning.
"They were good at-bats, but we came up empty," Girardi said.
Floyd was finished after seven innings, scattering nine hits but allowing only the two runs while walking none and fanning four.
With the Yankees flailing, their bullpen couldn't hold the game close. In the seventh, Jose Veras allowed back-to-back two-out doubles to Orlando Cabrera and Brian Anderson to bring around Chicago's fifth run, and Dan Giese allowed another run in the eighth.
The Yankees have two games remaining in their series against the White Sox (84-66) before playing a three-game weekend set against the Orioles to close out Yankee Stadium.
Bit by bit, the reality of the lights going out for good is setting in.
"You see the extra people here every day," Girardi said. "It's like more people want to get a taste of Yankee Stadium and come here for the last time. You understand that something historical is happening."