Detroit has won four in a row and will try for a four-game sweep of the White Sox on Thursday.
Fielder's home run came in the first inning, Austin Jackson added a solo blast in the second and Torii Hunter hit another one in the fifth. All three long balls came against John Danks (2-8), who gave up 11 hits in seven innings.
Anibal Sanchez (8-7) worked six scoreless innings for the win, allowing six hits and striking out five.
Chicago fell 20 games below .500 for the first time in six seasons. The White Sox had 11 hits and went 1-for-10 with men in scoring position.