This doubleheader was created after a postponement June 10 in the Tigers' most recent visit to U.S. Cellular Field, and rain is also forecast for Saturday.
A marquee duel is on tap in the afternoon. Scherzer (15-4, 3.13 ERA) can become the AL's first 16-game winner while Sale (10-3, 2.03) owns the league's best ERA.
"Two of the best pitchers in the league," Detroit manager Brad Ausmus told MLB's official website. "If it does rain, it's a possibility with those guys pitching, you might be able to get the game in under an hour."
Scherzer has posted a 0.96 ERA in winning his first four 2014 starts against Chicago. He struck out eight in a three-hitter in a 4-0 road victory June 12 in which Sale struck out 10 and gave up one run in seven innings.
Scherzer can become the first pitcher to improve to 5-0 against the White Sox (60-74) in a single season since Cleveland's Jim Kern in 1976. Kansas City's Paul Splittorff was the last to win his first five starts over Chicago in a season in 1973.
Jose Abreu, Adam Dunn, Alexei Ramirez and Dayan Viciedo have combined to go 10 for 49 with 15 strikeouts this year against Scherzer.
Sale is 0-2 with a 2.53 ERA in five starts in August as he tries to avoid going winless in a month as a starter for the second time in his career. He went 0-5 with a 3.19 ERA in six June outings last year.
The left-hander's loss to Scherzer this June marked his lone 2014 outing versus the Tigers (73-60). He is 3-5 with a 2.94 ERA in nine starts against them.
Victor Martinez has enjoyed the most success of any hitter with at least 15 at-bats against Sale, going 13 for 25 including a homer this year. Miguel Cabrera is 6 for 24 versus Sale.
Game 2 pits Detroit's Kyle Ryan against Chris Bassitt.
Ryan hails from the same place as Sale, Florida's Polk County, and he expects to have plenty of family at the game. The left-hander began at Double-A this year before going 3-0 with a 1.64 ERA in five starts for Triple-A Toledo.
Chicago fans may have hoped the club would call up heralded prospect Carlos Rodon, but they'll instead see Bassitt. The right-hander most recently pitched at Double-A Birmingham, where he was 3-1 with a 1.56 ERA in six starts.
"It's an opportunity for him," manager Robin Ventura said. "He's had more time and seasoning down there that I think this is just the right time to do it for him, and he's earned it."
Detroit opened this four-game series with Friday's 7-1 victory highlighted by four unearned runs as a result of two errors by Abreu.
''They gave us the advantage of a couple extra outs, and we took advantage of it,'' said Ausmus, whose club pulled within one-half game of first-place Kansas City in the Central.
Adam Eaton had three hits and has 11 in his last 18 at-bats against the Tigers.