| | | |
| March 26, 2022 | L | Columbus Crew 2 0 at Inter Miami CF II 2 | Final |
| April 3, 2022 | W | Columbus Crew 2 1 at Chicago Fire FC II 0 | Final |
| April 10, 2022 | W | Columbus Crew 2 1 at Philadelphia Union II 0 | Final |
| April 15, 2022 | W | Orlando City B 0 at Columbus Crew 2 2 | Final |
| April 24, 2022 | W | Toronto FC II 1 at Columbus Crew 2 2 | Final |
| May 8, 2022 | W | Columbus Crew 2 4 at New England Revolution II 0 | Final |
| May 15, 2022 | W | Columbus Crew 2 1 at New York City FC II 0 | Final |
| May 22, 2022 | W | Toronto FC II 2 at Columbus Crew 2 4 | Final |
| May 29, 2022 | | Rochester New York FC at Columbus Crew 2 | 2:00 p.m. |
| June 4, 2022 | | Columbus Crew 2 at Chicago Fire FC II | 6:00 p.m. |
| June 9, 2022 | | Inter Miami CF II at Columbus Crew 2 | 7:00 p.m. |
| June 19, 2022 | | Orlando City B at Columbus Crew 2 | 2:00 p.m. |
| June 24, 2022 | | Columbus Crew 2 at Rochester New York FC | 7:00 p.m. |
| July 2, 2022 | | Philadelphia Union II at Columbus Crew 2 | 7:00 p.m. |
| July 10, 2022 | | Columbus Crew 2 at Toronto FC II | 7:00 p.m. |
| July 16, 2022 | | FC Cincinnati 2 at Columbus Crew 2 | 7:00 p.m. |
| July 24, 2022 | | New England Revolution II at Columbus Crew 2 | 5:00 p.m. |
| July 31, 2022 | | Columbus Crew 2 at Philadelphia Union II | 7:00 p.m. |
| August 7, 2022 | | New York City FC II at Columbus Crew 2 | 5:00 p.m. |
| August 14, 2022 | | Columbus Crew 2 at FC Cincinnati 2 | 6:00 p.m. |
| August 20, 2022 | | Columbus Crew 2 at Orlando City B | 7:00 p.m. |
| September 4, 2022 | | Chicago Fire FC II at Columbus Crew 2 | 4:00 p.m. |
| September 11, 2022 | | Columbus Crew 2 at Inter Miami CF II | 7:00 p.m. |
| September 18, 2022 | | FC Cincinnati 2 at Columbus Crew 2 | 3:00 p.m. |
Columbus Crew 2 Schedule
