Brent Morel went 2-for-4 with a two-run homer 4 in the third test of a four-game set.
Mark Buehrle (12-9) pitched six solid innings of two-run ball to snap a personal three-game skid, as the White Sox won for the third time in four contests after dropping seven in a row. He scattered four hits while fanning two.
"Buehrle threw great," said Chicago manager Ozzie Guillen. "I think he needed that. The last couple of games were very rough for him. Having the type of game he had today was a bounce-back for him."
Ubaldo Jimenez (4-3) started strong with four scoreless innings, but allowed four runs over the next three frames to absorb the loss. He surrendered six hits while walking two and striking out seven.
"I feel bad myself because I want to push him, try to save our bullpen a little bit and give him an opportunity to win the ballgame," said Indians manager Manny Acta. "He couldn't do it, but I could have taken him out."
The White Sox got to Jimenez in the fifth when Tyler Flowers hit an opposite-field double over the head of Cleveland right fielder Kosuke Fukudome, which brought home Dayan Viciedo, who reached on a one-out single.
The White Sox added three runs in the seventh. Morel tied the contest with a double off the left-field wall to plate Viciedo, who walked. The relay throw from Alexei Ramirez was wide.
Chicago tacked on four more in the eighth on a two-run shot by Morel and a pair of solo home runs by Ramirez and Alex Rios.
The Indians added a two more runs in the eighth. Jason Kipnis lifted a sacrifice fly to plate Trevor Crowe, while Santana hit a bloop single to bring home Fukudome.
De Aza is 18-for-44 with six doubles, two triples, nine RBI and nine runs scored in 11 games against Cleveland...With his home run, Hafner is now one- hit shy of 1,000...The Indians have homered in 11 of their past 13 games and 19 of their last 24.