Baltimore's Nelson Cruz, second in the majors with 23 home runs, faces off against Chicago southpaw Chris Sale, who's held batters to a .171 average and has won six of seven decisions.
Meanwhile, White Sox rookie Jose Abreu -- just two long balls behind Cruz at 21 -- faces Orioles lefty Wei-Yin Chen, who's won seven of nine decisions and hasn't lost in eight starts since May 3.
Cruz is 3-for-8 with a homer in his career against Sale, who picked up his sixth win in his most recent start on Wednesday, when he allowed three runs in six innings of a 7-6 defeat of the San Francisco Giants.
He's faced the Orioles once in his career and was a 6-0 loser in Baltimore after allowing four runs in six innings in August 2012.
Orioles starters were 4-0 with a 2.29 earned run average on a just-completed six-game road trip and have combined for a 1.87 earned run average -- best in the majors -- since June 9.
"There's no rest for the weary because the big separator up here is the pitching you see," manager Buck Showalter said. "And we're going to see Sale (Monday) for the White Sox and if you dwell on it too long, there's another guy who's going to slap you back into reality."
Chen has received 6.59 runs of support per game from the Baltimore offense and is 4-0 with a 3.47 ERA dating back to his last loss. In his most recent start last Monday, he got a no-decision after allowing three runs in 6 2/3 innings against Tampa Bay.
Chen has never lost to the White Sox and has a 2.60 ERA in three starts against them.
Chicago's lefty slugger Adam Dunn is hitless against Chen in six at-bats.
On Sunday in Minnesota, Joe Mauer and Josh Willingham each knocked in two runs as the Twins beat the White Sox, 6-5, to complete a four-game sweep.
Abreu and Gordon Beckham each had two RBI for the White Sox, who got swept in a four-game set by Minnesota for the first time since June 9-12, 1994.
Chicago starter John Danks (6-6), who had won his previous three starts, allowed six runs on 10 hits with four walks over five-plus innings. He fell to 0-6 over his last eight starts against Minnesota.
In New York, Chris Tillman outpitched Masahiro Tanaka and the Orioles took down the Yankees, 8-0, in the rubber match of a three-game series.
Tillman (6-4) scattered four hits and four walks over seven scoreless innings while his teammates handed Tanaka just his second loss of the year.
Jonathan Schoop and Caleb Joseph both homered and drove in a pair of runs, while J.J. Hardy went 2-for-4 with a three-run double for Baltimore.
The Orioles went 4-3 against the White Sox last season.