Avisail Garcia went 5-for-5 with a three-run homer and seven RBI as the White Sox mauled the Tigers 17-7 at Comerica Park.
Yoan Moncada added four hits, including a solo homer, as part of Chicago's 25-hit attack.
James Shields pitched six innings of four-run ball to improve to 4-and-6 with the win.
Miguel Cabrera, Nick Castellanos, Jeimer Candelario and Ian Kinsler all went deep for the Tigers, who have lost six straight.
Chad Bell was rocked for nine hits and six runs in three-and-a-third frames to fall to 0-and-3.
The Tigers will try again tonight against the White Sox. It's the second of their four-game series at Comerica Park, with Anibal Sanchez slated to oppose Chicago's Carson Fulmer.
The Tigers have lost six straight games and are just 2-and-12 in the month of September. Detroit is now just one game ahead of Chicago for last in the AL Central.