| | | |
| February 22, 2025 | T | Colorado Rapids 0 at St. Louis City SC 0 | Final |
| March 1, 2025 | T | St. Louis City SC 0 at San Diego FC 0 | Final |
| March 9, 2025 | W | St. Louis City SC 3 at LA Galaxy 0 | Final |
| March 15, 2025 | W | Seattle Sounders FC 0 at St. Louis City SC 1 | Final |
| March 22, 2025 | L | St. Louis City SC 0 at Philadelphia Union 1 | Final |
| March 30, 2025 | L | Austin FC 1 at St. Louis City SC 0 | Final |
| April 5, 2025 | L | St. Louis City SC 0 at Sporting Kansas City 2 | Final |
| April 13, 2025 | L | Columbus Crew SC 2 at St. Louis City SC 1 | Final |
| April 19, 2025 | T | Vancouver Whitecaps FC 0 at St. Louis City SC 0 | Final |
| April 27, 2025 | T | St. Louis City SC 2 at Los Angeles FC 2 | Final |
| May 3, 2025 | L | St. Louis City SC 1 at Seattle Sounders FC 4 | Final |
| May 10, 2025 | L | San Diego FC 2 at St. Louis City SC 1 | Final |
| May 14, 2025 | T | Sporting Kansas City 2 at St. Louis City SC 2 | Final |
| May 17, 2025 | L | St. Louis City SC 0 at Minnesota United FC 3 | Final |
| May 24, 2025 | L | St. Louis City SC 0 at Colorado Rapids 1 | Final |
| May 31, 2025 | W | San Jose Earthquakes 1 at St. Louis City SC 2 | Final |
| June 8, 2025 | L | St. Louis City SC 1 at Portland Timbers 2 | Final |
| June 14, 2025 | T | LA Galaxy 3 at St. Louis City SC 3 | Final |
| June 25, 2025 | L | Orlando City SC 4 at St. Louis City SC 2 | Final |
| June 28, 2025 | L | St. Louis City SC 0 at Houston Dynamo FC 1 | Final |
| July 5, 2025 | L | St. Louis City SC 2 at Real Salt Lake 3 | Final |
| July 13, 2025 | W | Portland Timbers 1 at St. Louis City SC 2 | Final |
| July 19, 2025 | L | St. Louis City SC 0 at FC Dallas 3 | Final |
| July 26, 2025 | L | Minnesota United FC 2 at St. Louis City SC 1 | Final |
| August 9, 2025 | W | Nashville SC 1 at St. Louis City SC 3 | Final |
| August 16, 2025 | L | St. Louis City SC 2 at Chicago Fire FC 3 | Final |
| August 23, 2025 | L | St. Louis City SC 2 at Vancouver Whitecaps FC 3 | Final |
| August 30, 2025 | L | Houston Dynamo FC 3 at St. Louis City SC 2 | Final |
| September 6, 2025 | T | FC Dallas 1 at St. Louis City SC 1 | Final |
| September 13, 2025 | W | St. Louis City SC 2 at Club de Foot Montreal 0 | Final |
| September 20, 2025 | | St. Louis City SC at San Jose Earthquakes | 10:30 p.m. |
| September 27, 2025 | | Los Angeles FC at St. Louis City SC | 8:30 p.m. |
| October 4, 2025 | | St. Louis City SC at Austin FC | 8:30 p.m. |
| October 18, 2025 | | Real Salt Lake at St. Louis City SC | 9:00 p.m. |
St. Louis City SC Schedule
