| | | |
| 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 | W | Charlotte FC 2 at Columbus Crew SC 4 | Final |
| May 10, 2025 | T | Columbus Crew SC 2 at Philadelphia Union 2 | Final |
| May 14, 2025 | T | Columbus Crew SC 1 at Club de Foot Montreal 1 | Final |
| May 17, 2025 | T | FC Cincinnati 1 at Columbus Crew SC 1 | Final |
| May 24, 2025 | L | Columbus Crew SC 2 at Charlotte FC 3 | Final |
| May 28, 2025 | T | Nashville SC 2 at Columbus Crew SC 2 | Final |
| May 31, 2025 | L | Columbus Crew SC 1 at Inter Miami CF 5 | Final |
| June 14, 2025 | W | Vancouver Whitecaps FC 1 at Columbus Crew SC 2 | Final |
| June 25, 2025 | W | Atlanta United FC 1 at Columbus Crew SC 3 | Final |
| June 29, 2025 | W | Philadelphia Union 0 at Columbus Crew SC 1 | Final |
| July 6, 2025 | T | Columbus Crew SC 1 at Seattle Sounders FC 1 | Final |
| July 12, 2025 | W | Columbus Crew SC 4 at FC Cincinnati 2 | Final |
| July 16, 2025 | L | Columbus Crew SC 0 at Nashville SC 3 | Final |
| July 19, 2025 | W | D.C. United 1 at Columbus Crew SC 2 | Final |
| July 25, 2025 | L | Orlando City SC 3 at Columbus Crew SC 1 | Final |
| August 16, 2025 | T | Columbus Crew SC 1 at Toronto FC 1 | Final |
| August 23, 2025 | L | New England Revolution 2 at Columbus Crew SC 1 | Final |
| August 30, 2025 | T | Columbus Crew SC 0 at New York Red Bulls 0 | Final |
| September 13, 2025 | W | Columbus Crew SC 5 at Atlanta United FC 4 | Final |
| September 17, 2025 | L | Columbus Crew SC 2 at New York City FC 3 | Final |
| September 20, 2025 | T | Toronto FC 1 at Columbus Crew SC 1 | Final |
| September 27, 2025 | L | Columbus Crew SC 0 at Chicago Fire FC 2 | Final |
| October 4, 2025 | T | Columbus Crew SC 1 at Orlando City SC 1 | Final |
| October 18, 2025 | W | New York Red Bulls 1 at Columbus Crew SC 3 | Final |
| October 27, 2025 | L | Columbus Crew SC 0 at FC Cincinnati 1 (Playoff Gm. 1) | Final |
| November 2, 2025 | W | FC Cincinnati 0 at Columbus Crew SC 4 (Playoff Gm. 2) | Final |
| November 8, 2025 | | Columbus Crew SC at FC Cincinnati (Playoff Gm. 3) | 6:00 p.m. |
Columbus Crew SC Schedule
