The Indians jumped on top to an early lead and never looked back, scoring two runs in the second with a Karim Garcia single. Milton Bradley and Omar Vizquel, who scored on the play, reached base with an infield single to second and soft single to right center.
The Sox had their chance in the first to start things off with a D'Angelo Jimenez leadoff walk, but Jimenez was picked off first by Anderson. Tony Graffanino then doubled, followed by a Frank Thomas strikeout and Magglio Ordonez fly out to end the inning.
Paul Konerko connected for his first homer and fourth hit of the season in the second to cut the defecit in half. But the Indians came right back with a run off a Milton Bradley sacrifice fly to right, scoring Casey Blake.
Up 3-1, the Indians added a fourth run in the fourth with a Brandon Phillips solo home run, and a fifth run in the seventh off of reliever Kelly Wunsch. Wunsch came in for Garland after Garland gave up a leadoff double. After getting Bradley to fly out, Phillips stole third and then scored on a Vizquel sacrifice fly.
The Sox added their second and last run in the fifth with Josh Paul -- starting at catcher -- hitting a single and scoring two outs later on a Thomas double. Anderson was pulled after six innings in favor of Jose Santiago. Santiago threw 1 1/3 scoreless innings and Danys Baez picked up his third save with 1 2/3 scoreless innings.
The Sox failed on two other scoring chances. Once in the third with two men in scoring position and one out, which resulted in an Ordonez fly out and Jimenez getting thrown out at the plate after tagging up.
Then, with men on first and second in the eighth, Konerko and Carlos Lee were put out to end the inning.
Rick White relieved Wunsch with two outs in the seventh, ending the inning and throwing a scoreless 1-2-3 eighth. Joe Crede committed his third error of the season with a errant throw to first base in the seventh off a grounder.
The series' finale will be on Thursday at 6:05 p.m. CT with Mark Buehrle -- moving up to Esteban Loaiza's spot -- starting against 22-year-old righty Jason Davis. Loaiza will now start the opening series against the Tigers, followed by Josh Stewart and Bartolo Colon going in games two and three.