On a cold () and rainy evening, Morgan Ensberg's first-pitch home run off starter Mark Buehrle put the Astros on top in the second inning. The White Sox answered in the bottom of the second with two runs off Andy Pettitte on Joe Crede's RBI single with two on and Juan Uribe's sacrifice fly. Houston's Lance Berkman tied the game on a sacrifice fly in the third after a one-out triple, then hit a two-run double in the fifth to give the Astros a 4–2 lead. In the seventh, Dan Wheeler loaded the bases with a double by Juan Uribe, a walk to Tadahito Iguchi, and plate umpire Jeff Nelson's ruling that Jermaine Dye was hit by a pitched ball. The Astros brought in Chad Qualls, who promptly served up a grand slam to Paul Konerko on his first pitch, the 18th grand slam in the annals of the Fall Classic. In the top of the ninth, Sox closer Bobby Jenks blew the save on a game-tying pinch-hit single by José Vizcaíno. In the bottom of the ninth, Astros closer Brad Lidge gave up a one-out, walk-off home run—the 14th in Series history—to Scott Podsednik, giving Lidge his second loss in as many post-season appearances (his previous appearance was in Game 5 of 2005 National League Championship Series). Podsednik had not hit a single homer in the regular season, but this was his second of the post-season. This was the second time in World Series history where a grand slam and a walk-off home run were hit in the same game. The Oakland A's Jose Canseco (grand slam) and the Los Angeles Dodgers' Kirk Gibson (walk-off) in Game 1 of the 1988 World Series were the first to do it. Never before had a World Series grand slam and a World Series walk-off home run been hit by the same team in the same game. As of 2020, the grand slam by Konerko is the last World Series grand slam hit by the home team.