| 6 | Sat Apr 4 | at Atlanta | 7:30 PM | 1-1-3 | 4 PTS | Mercedes-Benz Stadium · Atlanta, GA |
| 7 | Sun Apr 12 | vsOrlando | 7:00 PM | 1-0-4 | 3 PTS | Lower.com Field · Columbus, OH |
| 8 | Sat Apr 18 | atNew England | 7:30 PM | 1-0-3 | 3 PTS | Gillette Stadium · Foxborough, MA |
| 9 | Wed Apr 22 | vsLA Galaxy | 7:30 PM | 1-2-2 | 5 PTS | Lower.com Field · Columbus, OH |
| 10 | Sat Apr 25 | vsPhiladelphia | 7:30 PM | 0-0-5 | 0 PTS | Lower.com Field · Columbus, OH |
| 11 | Sat May 2 | vsMinnesota | 7:30 PM | 1-2-2 | 5 PTS | Lower.com Field · Columbus, OH |
| 12 | Sun May 10 | atNYCFC | 4:30 PM | 3-1-1 | 10 PTS | Yankee Stadium · New York City, NY |
| 13 | Wed May 13 | atNew York | 7:30 PM | 2-1-2 | 7 PTS | Sports Illustrated Stadium · Harrison, NJ |
| 14 | Sat May 16 | atPhiladelphia | 7:30 PM | 0-0-5 | 0 PTS | Subaru Park · Chester, PA |
| 15 | Sun May 24 | vsAtlanta | 5:00 PM | 1-1-3 | 4 PTS | Lower.com Field · Columbus, OH |
| 17 | Wed Jul 22 | vsNYCFC | 7:30 PM | 3-1-1 | 10 PTS | Lower.com Field · Columbus, OH |
| 18 | Sat Jul 25 | vsCincinnati | 7:00 PM | 2-0-3 | 6 PTS | Lower.com Field · Columbus, OH |
| 19 | Sat Aug 1 | atMiami | 7:30 PM | 3-1-1 | 10 PTS | Chase Stadium · Fort Lauderdale, FL |
| 20 | Sat Aug 15 | atCharlotte | 7:30 PM | 2-2-1 | 8 PTS | Jerry Richardson Stadium · Charlotte, NC |
| 21 | Wed Aug 19 | vsMontreal | 7:30 PM | 1-0-4 | 3 PTS | Lower.com Field · Columbus, OH |
| 22 | Sat Aug 22 | atNashville | 8:30 PM | 4-1-0 | 13 PTS | GEODIS Park · Nashville, TN |
| 23 | Sat Aug 29 | vsNew England | 7:30 PM | 1-0-3 | 3 PTS | Lower.com Field · Columbus, OH |
| 24 | Sat Sep 5 | vsColorado | 7:30 PM | 3-0-2 | 9 PTS | Lower.com Field · Columbus, OH |
| 25 | Wed Sep 9 | atD.C. United | 7:30 PM | 2-1-2 | 7 PTS | Audi Field · Washington, D.C. |
| 26 | Sat Sep 12 | vsNew York | 7:30 PM | 2-1-2 | 7 PTS | Lower.com Field · Columbus, OH |
| 27 | Sat Sep 19 | atMontreal | 7:30 PM | 1-0-4 | 3 PTS | Stade Saputo · Montreal, QC |
| 28 | Sun Sep 27 | vsMiami | 7:00 PM | 3-1-1 | 10 PTS | Lower.com Field · Columbus, OH |
| 29 | Sat Oct 10 | atOrlando | 7:30 PM | 1-0-4 | 3 PTS | Inter&Co Stadium · Orlando, FL |
| 30 | Wed Oct 14 | vsCharlotte | 7:30 PM | 2-2-1 | 8 PTS | Lower.com Field · Columbus, OH |
| 31 | Sun Oct 18 | atCincinnati | 7:00 PM | 2-0-3 | 6 PTS | TQL Stadium · Cincinnati, OH |
| 32 | Sat Oct 24 | vsToronto | 2:30 PM | 2-1-2 | 7 PTS | Lower.com Field · Columbus, OH |
| 33 | Wed Oct 28 | atDallas | 8:30 PM | 2-2-1 | 8 PTS | Toyota Stadium · Frisco, TX |
| 34 | Sat Oct 31 | vsD.C. United | 2:00 PM | 2-1-2 | 7 PTS | Lower.com Field · Columbus, OH |
| 35 | Sat Nov 7 | atChicago | 4:00 PM | 2-1-2 | 7 PTS | Soldier Field · Chicago, IL |
