The Tigers sent seven men to the plate in the first inning, bringing across three runs against Cleveland right-hander Gavin Williams.
Akil Baddoo homered on Williams' second pitch of the game — a four-seam fastball in the middle of the zone — driving it 412 feet into over the wall in right-center field.
With two out, Spencer Torkelson doubled to center and scored on Kerry Carpenter's single to right. Carpenter came around to score when Miguel Cabrera doubled on the first pitch he saw for a 3-0 lead.
Cleveland struck back in the bottom of the first when Jose Ramirez hit a one-out double and came around to score on Oscar Gonzalez's single to left.
Skubal, making just his eighth start of the season after returning from flexor-tendon surgery last August, settled down nicely after the first. He retired 12 Guardians hitters in a row in one stretch and set down 14 of the last 15 batters he faced.
The Tigers had a potential run erased in the fifth on a challenge by Cleveland manager Terry Francona. Carpenter was initially called safe at first after his sharp grounder was booted by first baseman Gabriel Arias, who flipped to Williams covering the base late. Baddoo would have scored from third on the play, but the challenge erased the run.
Detroit tacked on an insurance run in the top of the ninth when Jake Rogers connected for a 397-foot solo home run to right center.
The Guardians got that run back in the bottom of the inning after Steven Kwan led off with a triple against Tigers closer Jason Foley, and scored on Gonzalez's grounder to second. Foley finished for his sixth save.
Skubal (3-2) worked six innings, allowing three hits and a walk while striking out seven. Williams (1-4) allowed three runs and six hits over five innings with two walks and four strikeouts.
The series opener was rained out on Thursday night, setting up a traditional doubleheader for Friday.
—Field Level Media