AL Central-leading Chicago seeks a four-game split with Baltimore, which looks keep its hold on the league's second wild-card spot.
The White Sox won for only the second time in seven meetings with the Orioles after Wednesday's 8-1 rout at Camden Yards, scoring four runs in the first inning. Alexei Ramirez went 3 for 4 with two RBIs and a pair of runs scored, and Dylan Axelrod earned the win with 7 1-3 solid innings.
Chicago (72-57), which dropped the first two of this set, increased its division lead over Detroit to three games ahead of a critical three-game series with the Tigers beginning Friday night.
''(I) put forth my best effort and (got) this team back on a winning track that hopefully carries into (Thursday) and into Detroit as well,'' Axelrod said before being optioned back to Double-A Birmingham.
Baltimore (71-58), meanwhile, had its hold on the league's second wild-card spot trimmed to one-half game over Tampa Bay with the defeat, and it remained 3 1/2 games behind the AL East-leading New York Yankees, who also lost Wednesday.
The Orioles, whose Nos. 2-4 hitters went 0 for 10, have three games at Yankee Stadium starting Friday.
The White Sox will look to win for the eighth time in 10 games with help from Jose Quintana, who has been a pleasant surprise in his rookie season.
Quintana (5-2, 2.86 ERA), though didn't have his best outing Saturday against Seattle, giving up three runs and walking four in 5 2-3 innings of Chicago's 5-4 win after going 1-1 with a 2.61 ERA over his previous three starts.
It also marked the first time the left-hander failed to pitch at least into the seventh inning in seven outings, though both catcher A.J. Pierzynski and manager Robin Ventura were ejected in the third inning for questioning umpire Lance Barrett's strike zone in that game.
"That's what teammates are for," Quintana told the team's official website. "A.J. and Robin coming out and sticking up for myself, for the team. I know things like that end up happening but I'm just glad they stood up."
Quintana will be opposed by Zach Britton, who has been pitching better of late.
Britton (3-1, 5.59) has been solid while winning his last two starts, tossing seven scoreless innings against Detroit on Aug. 18 and giving up two runs in 6 2-3 innings versus Toronto on Friday.
The left-hander has lowered his ERA nearly three runs over his last three outings.
"I would say (I am) a little more confident," Britton told the team's official website. "I feel good out on the mound. Right now I'm executing pitches a lot better. There's still some room for improvement, which is good."
Britton beat the White Sox in his only career start against them, giving up one run in six innings May 1, 2011.
Ventura said Pierzynski, mired in a 0-for-14 slump, will be back in the lineup after getting Wednesday off.