American League Central-leading Minnesota (78-70) won for the third time in four games while sending Chicago to its 11th loss in 14 games.
Lewis provided all the offense the Twins would need. With two outs and the bases loaded in the second inning, he drove a 2-1 pitch from White Sox rookie right-hander Jesse Scholtens into the left field bleachers.
Lewis notched his fifth career grand slam overall in his 66th career, the fastest any player has achieved that milestone, according to ESPN Stats & Info.
Twins right-hander Bailey Ober benefited from the blast to pick up his first win since July 18, a span of eight starts. Coming off a brief demotion to Triple-A to help manage his innings load, Ober (7-6) scattered two runs and five hits in five innings while striking out eight and walking none.
Ober allowed just one extra-base hit, a two-run homer off the bat of Elvis Andrus in the fifth. That drew the White Sox (56-92) within 6-2, as Minnesota had extended its early lead with runs in the third and fourth innings.
Ryan Jeffers had two hits and two RBIs for Minnesota. Max Kepler, Carlos Correa, Willi Castro and Wallner each contributed two hits and an RBI. Scholtens (1-9) yielded six runs, five earned, and seven hits in four innings. He walked three and struck out five.
Pitching for the seventh time in the past 10 games, White Sox reliever Bryan Shaw allowed one hit and struck out two in two innings of scoreless relief.
Andrew Vaughn singled twice for the White Sox to stretch his hitting streak to five games.
Minnesota is 8-3 against Chicago this season.
—Field Level Media