| | | |
| March 9, 2025 | L | Columbus Crew 2 1 at Orlando City B 2 | Final |
| March 14, 2025 | L | Columbus Crew 2 0 at New York City FC II 2 | Final |
| March 23, 2025 | L | Columbus Crew 2 2 at Inter Miami CF II 4 | Final |
| April 6, 2025 | T | Crown Legacy FC 1 at Columbus Crew 2 1 | Final (PK 4-3) |
| April 23, 2025 | T | Columbus Crew 2 2 at New England Revolution II 2 | Final (PK 1-4) |
| April 27, 2025 | | Chattanooga FC at Columbus Crew 2 | 3:00 p.m. |
| May 11, 2025 | | Columbus Crew 2 at Philadelphia Union II | 3:00 p.m. |
| May 18, 2025 | | FC Cincinnati 2 at Columbus Crew 2 | 3:00 p.m. |
| May 25, 2025 | | New York Red Bulls II at Columbus Crew 2 | 6:00 p.m. |
| June 1, 2025 | | Columbus Crew 2 at Chicago Fire FC II | 2:00 p.m. |
| June 12, 2025 | | New York City FC II at Columbus Crew 2 | 6:00 p.m. |
| June 21, 2025 | | Philadelphia Union II at Columbus Crew 2 | 3:00 p.m. |
| June 28, 2025 | | Carolina Core FC at Columbus Crew 2 | 6:00 p.m. |
| July 5, 2025 | | New England Revolution II at Columbus Crew 2 | 3:00 p.m. |
| July 13, 2025 | | Columbus Crew 2 at Atlanta United 2 | 7:30 p.m. |
| July 18, 2025 | | Columbus Crew 2 at Huntsville City Football Club | 8:00 p.m. |
| July 27, 2025 | | Toronto FC II at Columbus Crew 2 | 6:00 p.m. |
| July 31, 2025 | | New York Red Bulls II at Columbus Crew 2 | 6:00 p.m. |
| August 3, 2025 | | Columbus Crew 2 at Chicago Fire FC II | 2:00 p.m. |
| August 8, 2025 | | Columbus Crew 2 at New England Revolution II | 7:00 p.m. |
| August 17, 2025 | | Orlando City B at Columbus Crew 2 | 3:00 p.m. |
| August 22, 2025 | | Columbus Crew 2 at New York City FC II | 7:30 p.m. |
| August 31, 2025 | | Columbus Crew 2 at New York Red Bulls II | 5:00 p.m. |
| September 7, 2025 | | Inter Miami CF II at Columbus Crew 2 | 3:00 p.m. |
| September 14, 2025 | | Philadelphia Union II at Columbus Crew 2 | 3:00 p.m. |
| September 19, 2025 | | Columbus Crew 2 at Toronto FC II | 7:00 p.m. |
| September 25, 2025 | | Columbus Crew 2 at FC Cincinnati 2 | 7:30 p.m. |
| October 5, 2025 | | Chicago Fire FC II at Columbus Crew 2 | 1:00 p.m. |
Columbus Crew 2 Schedule
