| 6 | Sat Apr 4 | at NYCFC | 7:30 PM | 3-1-1 | 10 PTS | Yankee Stadium · New York City, NY |
| 7 | Sat Apr 11 | atDallas | 8:30 PM | 2-2-1 | 8 PTS | Toyota Stadium · Frisco, TX |
| 8 | Sat Apr 18 | atSeattle | 9:30 PM | 3-1-1 | 10 PTS | Costello Athletic Center · Lowell, MA |
| 10 | Sat Apr 25 | vsSan Jose | 8:30 PM | 4-0-1 | 12 PTS | Energizer Park · St. Louis, MO |
| 11 | Sun May 3 | atAustin | 5:30 PM | 1-2-2 | 5 PTS | Q2 Stadium · Austin, TX |
| 12 | Sat May 9 | atColorado | 9:30 PM | 3-0-2 | 9 PTS | Dick's Sporting Goods Park · Commerce City, CO |
| 13 | Wed May 13 | vsLAFC | 8:30 PM | 4-1-0 | 13 PTS | Energizer Park · St. Louis, MO |
| 14 | Sat May 16 | atD.C. United | 7:30 PM | 2-1-2 | 7 PTS | Audi Field · Washington, D.C. |
| 15 | Sat May 23 | vsAustin | 2:30 PM | 1-2-2 | 5 PTS | Energizer Park · St. Louis, MO |
| 16 | Thu Jul 16 | vsKansas City | 8:30 PM | 1-1-3 | 4 PTS | Energizer Park · St. Louis, MO |
| 17 | Wed Jul 22 | atLA Galaxy | 10:30 PM | 1-2-2 | 5 PTS | Dignity Health Sports Park · Carson, CA |
| 18 | Sat Jul 25 | vsColorado | 8:30 PM | 3-0-2 | 9 PTS | Energizer Park · St. Louis, MO |
| 19 | Sat Aug 1 | vsSalt Lake | 8:30 PM | 3-1-1 | 10 PTS | Energizer Park · St. Louis, MO |
| 20 | Sat Aug 15 | atSan Jose | 10:30 PM | 4-0-1 | 12 PTS | PayPal Park · San Jose, CA |
| 21 | Wed Aug 19 | atKansas City | 8:00 PM | 1-1-3 | 4 PTS | Children's Mercy Park · Kansas City, KS |
| 22 | Sat Aug 22 | vsHouston | 8:30 PM | 2-0-2 | 6 PTS | Energizer Park · St. Louis, MO |
| 23 | Sun Aug 30 | vsDallas | 7:00 PM | 2-2-1 | 8 PTS | Energizer Park · St. Louis, MO |
| 24 | Sat Sep 5 | atVancouver | 10:30 PM | 4-0-1 | 12 PTS | BC Place · Vancouver, BC |
| 25 | Wed Sep 9 | atPortland | 10:30 PM | 1-1-3 | 4 PTS | Providence Park · Portland, OR |
| 26 | Sat Sep 12 | vsMinnesota | 8:30 PM | 1-2-2 | 5 PTS | Energizer Park · St. Louis, MO |
| 27 | Sat Sep 19 | vsToronto | 8:30 PM | 2-1-2 | 7 PTS | Energizer Park · St. Louis, MO |
| 28 | Sat Sep 26 | atNew York | 7:30 PM | 2-1-2 | 7 PTS | Sports Illustrated Stadium · Harrison, NJ |
| 29 | Sun Oct 11 | vsLA Galaxy | 7:00 PM | 1-2-2 | 5 PTS | Energizer Park · St. Louis, MO |
| 30 | Wed Oct 14 | vsVancouver | 8:30 PM | 4-0-1 | 12 PTS | Energizer Park · St. Louis, MO |
| 31 | Sat Oct 17 | atMinnesota | 4:30 PM | 1-2-2 | 5 PTS | Allianz Field · Saint Paul, MN |
| 32 | Sat Oct 24 | atSalt Lake | 8:30 PM | 3-1-1 | 10 PTS | America First Field · Sandy, UT |
| 33 | Wed Oct 28 | vsPortland | 8:30 PM | 1-1-3 | 4 PTS | Energizer Park · St. Louis, MO |
| 34 | Sun Nov 1 | vsSan Diego | 3:00 PM | 3-2-0 | 11 PTS | Energizer Park · St. Louis, MO |
| 35 | Sat Nov 7 | atHouston | 7:00 PM | 2-0-2 | 6 PTS | Shell Energy Stadium · Houston, TX |
