| 1. Round | 23/02/2025 | St. Louis City SC | - | Colorado Rapids | 0:0 | ||||
| 2. Round | 02/03/2025 | San Diego FC | - | St. Louis City SC | 0:0 | ||||
| 3. Round | 09/03/2025 | Los Angeles Galaxy | - | St. Louis City SC | 0:3 | ||||
| 5. Round | 22/03/2025 | Philadelphia Union | - | St. Louis City SC | 1:0 | ||||
| 6. Round | 30/03/2025 | St. Louis City SC | - | Austin FC | 0:1 | ||||
| 7. Round | 06/04/2025 | Sporting Kansas City | - | St. Louis City SC | 2:0 | ||||
| 8. Round | 14/04/2025 | St. Louis City SC | - | Columbus Crew | 1:2 |  |
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| 9. Round | 20/04/2025 | St. Louis City SC | - | Vancouver Whitecaps | 0:0 |  |
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| 10. Round | 28/04/2025 | Los Angeles FC | - | St. Louis City SC | 2:2 | ||||
| 11. Round | 04/05/2025 | Seattle Sounders | - | St. Louis City SC | 4:1 | ||||
| 12. Round | 11/05/2025 | St. Louis City SC | - | San Diego FC | 1:2 | ||||
| 13. Round | 15/05/2025 | St. Louis City SC | - | Sporting Kansas City | 2:2 | ||||
| 14. Round | 18/05/2025 | Minnesota United FC | - | St. Louis City SC | 3:0 | ||||
| 15. Round | 25/05/2025 | Colorado Rapids | - | St. Louis City SC | 1:0 | ||||
| 17. Round | 31/05/2025 | St. Louis City SC | - | San Jose Earthquakes | 2:1 | |
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| 18. Round | 09/06/2025 | Portland Timbers | - | St. Louis City SC | 2:1 |
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