The game, which took only one hour and 39 minutes, was the quickest game ever played at U.S. Cellular Field.
Paul Konerko homered twice to account for all of the White Sox runs. Chicago has won won four of its last five games.
Ichiro Suzuki had all three hits for the Mariners.
Buehrle (2-1), who did not allow a run in eight innings on Opening Day, struck out 12 and walked only one.