Alex Rios hit a two-run homer in the fifth off Indians starter Zach McAllister that proved to be the difference in the White Sox 3-2 win over the Tribe on Wednesday.
Jeff Keppinger had two hits for the White Sox and also drove in the other Chicago run.
The Indians tried to rally in the sixth with two runs, but they fell short.
McAllister went five-and-two-thirds giving up three runs on five hits striking out four.
The Tribe will have Thursday off then travel to Kansas City for a weekend series with the Royals. Scott Kazmir will take the mound for the Indians against Ervin Santana.