The lead, which was made with one run in the first -- coming off a D'Angelo Jimenez error -- and another in the third, lasted up until Boston's first reliever, Ryan Rupe, gave up a three-run homer to Joe Crede.
The first-inning error by Jimenez came on Bill Mueller grounder, which he failed to field cleanly. Two batters later, after Nomar Garciaparra's single, Manny Ramirez drove in the run with a sacrifice fly. Ramirez drove in the second and final run for the Red Sox with a homer.
The White Sox cut the deficit to 2-1 with a RBI-single by Josh Paul in the fifth, scoring Konerko (walk).
Then came Crede's homer, which put the White Sox up 4-2, giving Buehrle a two-run lead to work with. Buehrle went out to pitch through the eighth inning, with Tom Gordon picking up the save with a scoreless ninth.
In eight innings, Buehrle walked one and struck out three, throwing 91 pitches. One of the two runs were unearned.
Game two of the series will be Tuesday night at 7:05 p.m. CT, with Bartolo Colon going up against Tim Wakefield. The game will be televised on Fox Sports Net Chicago.