The home runs were the 556th and 557th of Thome's 17-year career and moved him within six of Reggie Jackson for 12th place. It was his 43rd multihomer game.
It was 3-all in the fifth when Orioles starter Jason Berken walked Scott Podsednik and Jermaine Dye before hanging a 2-0 pitch that Thome lined over the right-field fence.
After Adam Jones' two-run homer off White Sox reliever Scott Linebrink made it 6-5, two Baltimore relievers loaded the bases in the sixth by walking Podsednik and Alexei Ramirez and hitting Dye with a pitch. Thome then sent Danys Baez's waist-high offering far over the center-field wall
- a shot the White Sox estimated at 448 feet - for his ninth career grand slam.
Popular for his on-field accomplishments and off-field charity work, Thome got a standing ovation, emerged from the dugout and waved to the fans.
Paul Konerko also homered for the White Sox, who moved within 2 1/2 games of first-place Detroit in the AL Central. John Danks (8-6) allowed three runs in five innings for Chicago, which is 31-21 since starting the season 15-22.
Nick Markakis hit a two-run homer for the Orioles, who have a league-worst 14-28 road record.
Berken (1-7) gave up six runs in 4 1-3 innings and is winless since earning a victory in his May 26 major league debut.
Podsednik reached base five times (three singles, two walks) and scored three runs.