Ramirez is the first pitcher to allow four straight homers in his debut. Yoán Moncada, Yasmani Grandal, José Abreu and Eloy Jiménez connected during a six-run fifth inning.
Ramirez took the mound in the fifth with Chicago leading 1-0. He struck out Luis Robert to start, but things went south quickly. After two singles, a caught stealing and a walk, Moncada smacked a three-run homer to right.
Grandal followed with another drive into the right-field seats, and then Abreu and Jimenez each homered to left.
Manager Mike Shildt replaced Ramirez with Seth Elledge, and he struck out Edwin Encarnacion on three straight pitches to end the inning.
Ramirez is among the players promoted by the Cardinals following a COVID-19 outbreak that stalled St. Louis’ season for 2 1/2 weeks. The club returned to action Saturday with a doubleheader sweep over Chicago.
Ramirez, a 25-year-old right-hander, split last season between Double-A and Triple-A.
It was the 10th time in major league history a team hit four straight homers. The only other time the White Sox did it was on Aug. 14, 2008 against Kansas City, when Jim Thome, Paul Konerko, Alexei Ramirez and Juan Uribe connected.
The White Sox got another solid start from Dallas Keuchel (3-2) and won for just the third time in 11 home games.
Keuchel gave up two runs and four hits in 5 2/3 innings. The 2015 AL Cy Young Award winner exited after Matt Carpenter hit a two-run single.
St. Louis’ Dakota Hudson (0-2) held the White Sox to a run and two hits over four innings in his first start since July 26. But the Cardinals fell to 4-4. Every other team had played at least 14 games coming into the day.
Cardinals: LHP Austin Gomber could rejoin the club Monday and start the second game of a doubleheader against the Chicago Cubs at Wrigley Field, Shildt said. He was placed on the injured list because he came up as a potential concern in contact tracing, though he did not test positive for COVID-19.
White Sox: RHP Reynaldo López (shoulder soreness), who threw Friday, is scheduled for another session Monday.
Cardinals: The Cardinals head to the North Side for five games in three days against the Cubs, starting with a doubleheader on Monday. St. Louis will go with LHP Kwang Hyun Kim (0-0, 9.00 ERA) in the opener and a bullpen start in the nightcap. The Cubs hadn't announced their starters.
White Sox: LHP Gio González (0-1, 6.61) gets another shot at the Tigers and his first Chicago win. The veteran, who was drafted by the White Sox in 2004 and signed with them in the offseason, wasn't thrilled when he got pulled one out shy of the victory Tuesday after holding Detroit to two runs in 4 2/3 innings. LHP Matthew Boyd (0-2, 10.24) starts for the Tigers.