| | | |
| February 22, 2025 | W | Chicago Fire FC 2 at Columbus Crew SC 4 | Final |
| March 1, 2025 | W | Columbus Crew SC 1 at New England Revolution 0 | Final |
| March 8, 2025 | T | Houston Dynamo FC 0 at Columbus Crew SC 0 | Final |
| March 15, 2025 | T | Columbus Crew SC 1 at San Diego FC 1 | Final |
| March 22, 2025 | T | New York City FC 0 at Columbus Crew SC 0 | Final |
| March 29, 2025 | W | Columbus Crew SC 2 at D.C. United 1 | Final |
| April 5, 2025 | W | Club de Foot Montreal 1 at Columbus Crew SC 2 | Final |
| April 13, 2025 | W | Columbus Crew SC 2 at St. Louis City SC 1 | Final |
| April 19, 2025 | L | Inter Miami CF 1 at Columbus Crew SC 0 | Final |
| April 26, 2025 | W | San Jose Earthquakes 1 at Columbus Crew SC 2 | Final |
| May 3, 2025 | | Charlotte FC at Columbus Crew SC | 7:30 p.m. |
| May 10, 2025 | | Columbus Crew SC at Philadelphia Union | 7:30 p.m. |
| May 14, 2025 | | Columbus Crew SC at Club de Foot Montreal | 7:30 p.m. |
| May 17, 2025 | | FC Cincinnati at Columbus Crew SC | 7:00 p.m. |
| May 24, 2025 | | Columbus Crew SC at Charlotte FC | 7:30 p.m. |
| May 28, 2025 | | Nashville SC at Columbus Crew SC | 8:00 p.m. |
| May 31, 2025 | | Columbus Crew SC at Inter Miami CF | 7:30 p.m. |
| June 14, 2025 | | Vancouver Whitecaps FC at Columbus Crew SC | 7:30 p.m. |
| June 25, 2025 | | Atlanta United FC at Columbus Crew SC | 7:30 p.m. |
| June 29, 2025 | | Philadelphia Union at Columbus Crew SC | 6:00 p.m. |
| July 6, 2025 | | Columbus Crew SC at Seattle Sounders FC | 5:00 p.m. |
| July 12, 2025 | | Columbus Crew SC at FC Cincinnati | 7:30 p.m. |
| July 16, 2025 | | Columbus Crew SC at Nashville SC | 8:30 p.m. |
| July 19, 2025 | | D.C. United at Columbus Crew SC | 7:30 p.m. |
| July 25, 2025 | | Orlando City SC at Columbus Crew SC | 7:30 p.m. |
| August 9, 2025 | | Columbus Crew SC at New York City FC | 7:30 p.m. |
| August 16, 2025 | | Columbus Crew SC at Toronto FC | 7:30 p.m. |
| August 23, 2025 | | New England Revolution at Columbus Crew SC | 7:30 p.m. |
| August 30, 2025 | | Columbus Crew SC at New York Red Bulls | 7:30 p.m. |
| September 13, 2025 | | Columbus Crew SC at Atlanta United FC | 7:30 p.m. |
| September 20, 2025 | | Toronto FC at Columbus Crew SC | 7:30 p.m. |
| September 27, 2025 | | Columbus Crew SC at Chicago Fire FC | 8:30 p.m. |
| October 4, 2025 | | Columbus Crew SC at Orlando City SC | 7:30 p.m. |
| October 18, 2025 | | New York Red Bulls at Columbus Crew SC | 6:00 p.m. |
Columbus Crew SC Schedule
