Upton, who entered the game hitting only .186, had a two-run homer and three singles after striking out in his first two at-bats. The single in the 11th off Ryan Webb (1-5) drove in pinch-runner Paul Janish from second base.
Luis Ayala (1-1) pitched a scoreless 11th.
With two outs, Webb walked Dan Uggla, bringing Upton to the plate.
Michael Kopech, the top pitching prospect in the White Sox organization, is expected to be ready for spring training in 2020 after having Tommy John surgery.
White Sox slugger Jose Abreu has been released from a Cleveland hospital after undergoing treatment for an infection in his right thigh.
Tommy Pham homered twice while extending his on-base streak to 21 games and the late-surging Tampa Bay Rays completed a three-game sweep of the Texas Rangers with a 9-3 victory Wednesday.
Tommy Pham hits a pair of solo home runs to help lift Tampa Bay past Texas.
Cleveland Indians right-hander Trevor Bauer will start against the Boston Red Sox on Friday when he comes off the disabled list, manager Terry Francona said Wednesday. Francona hopes Bauer will be able to join the team's playoff rotation.
Mookie Betts, who sat out Tuesday's series opener vs. the Yankees after injuring his side while making a throw on Sunday, will serve as DH for the Red Sox on Wednesday.