With the Yankees primed to return on Friday to Cleveland, the site of Chamberlain's infamous Game 2 meltdown in last year's American League Division Series, this was a new setback they could have done without.
"It's going to happen -- are you shocked?" Yankees manager Joe Girardi said. "Sometimes the expectations are extremely high. He's thrown the ball well, and it happens. ... He'll be fine. He'll bounce back. He's given up a run before in his life."
New York rallied from behind to tie the game in the seventh inning, long after a 51-minute rain delay forced the club to lift starter Phil Hughes and turn the game over to the bullpen in the third inning.
Chamberlain was working a second inning of relief only because right-hander Kyle Farnsworth slipped on a soft landing patch of the mound, telling Girardi he felt something in his right elbow as he delivered his final pitch of the seventh inning.
"The weather wasn't our friend tonight," Girardi said.
After waiting out a 34-minute rain delay before the game's first pitch, the 21-year-old Hughes started for New York and fired two scoreless innings, allowing one hit, but he made his exit after the clubs waited out the other delay before the bottom of the third inning, with heavy downpours passing through the area.
While Hughes said he could take positives from the aborted outing -- he compared it to a "good, short bullpen" -- he felt as though his sharp fastball and curveball had somewhat gone to waste, as he was left still looking for his first win of the year after five starts.
Hughes said he did not campaign to stay in the game, since Girardi and pitching coach Dave Eiland had already made up their minds not to bring him back out.
"I felt like I was commanding the ball better," Hughes said. "I haven't felt like that in a while. It's kind of unfortunate I could only go out there for two innings."
Right-hander Ross Ohlendorf came on and threw a scoreless third inning, but the makeshift long reliever was roughed up for five runs on five hits as the White Sox batted around in the fourth -- an inning highlighted by consecutive run-scoring hits from Paul Konerko, Jermaine Dye and Pierzynski.
Ohlendorf said that he felt the difference between the third and fourth innings was a lack of sink on his pitches.
"It was certainly too hittable," Ohlendorf said.
Jim Thome tacked on a two-run home run, the 513th of his career, facing LaTroy Hawkins in the bottom of the sixth to extend Chicago's lead.
While the Yankees pulled Hughes early, Chicago starter Gavin Floyd stayed in through the delay. He allowed three runs in the top of the third, led by Bobby Abreu's two-run double and a Derek Jeter sacrifice fly.
"I told him, 'Don't be a hero tonight,'" White Sox manager Ozzie Guillen said of Floyd. "I don't want to get blamed if something happens to [Floyd], but I believed in him, and he went back out there."
Cabrera brought the Yankees back with a two-run homer, his fourth of the season, facing Floyd in the sixth after a Jason Giambi double. Floyd allowed five runs on five hits over six innings, walking four and striking out four.
New York tied the game in the seventh against the Chicago bullpen, as Abreu stroked a two-out single off Matt Thornton and Hideki Matsui walked. Scott Linebrink came on, and Morgan Ensberg poked a 3-2 pitch back up the middle for a run-scoring single, bringing Abreu home.
The Yankees had a two-on, one-out chance in the ninth inning. With left-hander Boone Logan working his second inning, Jeter opened with a sharp single up the middle.
Matsui followed with a one-out single, drawing Bobby Jenks on in relief, but pinch-hitter Jorge Posada grounded into an inning-ending 4-6-3 double play.
That set the scene for Chamberlain's troubles in the ninth, dealing the Yankees their first walk-off loss of the season.
"They did what they were supposed to do," Chamberlain said. "They had good at-bats and challenged. They got the best of me this time."