All-Star first baseman Joey Votto homered for Cincinnati, which took the opener of the team's annual battle for the Ohio Cup and sent the AL Central leaders to their third straight loss.
Cincinnati improved to 9-2 against American League teams and is 37-36 since interim manager Jim Riggleman replaced Bryan Price on April 19.
DeSclafani (4-1) held the Indians to five hits. Yonder Alonso's solo homer broke Cleveland's 17-inning scoreless streak in the fourth.
DeSclafani, making his seventh start, strained his left oblique in spring training and began the season on the 60-day disabled list. The right-hander missed last season because of a sprained elbow ligament.
Votto hit a fifth-inning home run off Mike Clevinger (7-4), who matched a career high with 11 strikeouts in six-plus innings. Cleveland's right-hander allowed five runs.
Jason Kipnis hit a two-run homer in the ninth off Amir Garrett, cutting the lead to 7-3. Raisel Iglesias relieved with two on and one out. Francisco Lindor's sacrifice fly and Michael Brantley's RBI double made it a two-run game.
Iglesias struck out All-Star Jose Ramirez on three pitches for his 18th save.
Schebler had an RBI single in the seventh and a two-run homer in the ninth.
Tucker Barnhart's RBI double put Cincinnati ahead in the second. Jesse Winker had an RBI double in the fourth that was followed by Barnhart's run-scoring single.
Schebler singled on the game's first pitch, but was nearly picked off with Jose Peraza batting. Schebler went back to the bag standing up on Clevinger's pickoff throw and was called out by James Hoye. The Reds challenged the play and the call was overturned.
Clevinger struck out the next two hitters and Tyler Naquin robbed Scooter Gennett of a run-scoring hit with a diving catch on the warning track in right.
Barnhart's double scored Eugenio Suarez, who drew a leadoff walk in the second. Greg Allen crashed into the center field wall while making a leaping catch of Adam Duvall's drive.
Votto hit his 266th career homer, moving into second place among Canadian-born players in MLB history and passed Matt Stairs. Larry Walker holds the record with 383.
Jason Kipnis hit a two-run homer in the ninth off Amir Garrett. Raisel Iglesias
TRAINER'S ROOM
Indians: LHP Andrew Miller (sore right knee) might face hitters in a simulated game Saturday. He threw 29 pitches in a bullpen session Monday and will throw off the mound again Wednesday. Miller has been out since May 26.
UP NEXT
Reds RHP Sal Romano (5-8, 5.40 ERA) takes on Indians RHP Trevor Bauer (8-6, 2.45 ERA). Bauer, named to the All-Star team Sunday, is seeking his MLB-record seventh straight quality start with at least eight strikeouts and zero homers allowed.
