Buehrle did have the lead at one point, up 1-0 after a first-inning RBI groundout by Magglio Ordonez, but gave up the tying run in the second off a Brian Jordan homer and the eventual winning run in the third off a RBI-single by Paul Lo Duca.
The inning consisted of three plays between home plate and the pitchers mound. The first happening on a softly hit ball by Cesar Izturis for an infield single that ended with him at second after Miguel Olivo committed a throwing error.
After opposing starter Kazuhisa Ishii sacrificed Izturis to third with a bunt, David Roberts hit a comebacker to Buehrle, who then caught Izturis in a rundown for the second out. Roberts made it to third on the play, setting up Lo Duca's single.
That was all Buehrle gave up, but it was also all too much as Ishii held the Sox to just two hits after the first inning, leaving after the seventh.
Ishii struck out nine and walked two. Relievers Paul Quantrill, Tom Martin and Paul Shuey pitched the eighth inning, leaving Eric Gagne to pick up his 21st save with a 1-2-3 ninth.
The Sox scored their lone run with a Jose Valentin walk, Frank Thomas double and Ordonez groundout to second, scoring Valentin from third.
Two of the Sox' four hits on offense were from Joe Crede, who was hitless in his last 21 at bats heading into the game, with the other two coming from Thomas and Olivo (double). Tony Graffanino had a rough game after going 2-5 on Thursday, going 0-4 with three strikeouts.
After Buehrle, who is now winless in his last 11 starts, Tom Gordon pitched two scoreless innings, striking out two.
The Sox will play game two of the set on Saturday at 9:10 p.m. CT. Bartolo Colon is scheduled to pitch against Andy Ashby. The game will be televised on WGN.