Ryan LaMarre's second-inning solo homer broke a 3-all tie and the White Sox went on to double up the Tigers 6-3 in Detroit.
Jose Abreu doubled home two runs for Chicago, which had lost three in-a-row and six of its previous seven games.
Starter Lucas Giolito got out of a bases-loaded, no-out jam in the sixth to earn the win.
Blaine Hardy took the loss for Detroit.
Detroit had won three-of-four.
Detroit scored all of its runs in the first inning as Victor Martinez knocked in two with a double and Jim Adduci singled in another.
In this afternoon's series finale, Jordan Zimmermann opposes Chicago's Carlos Rodon.