The Purdue Boilermakers return to the football field in 2022 for a 12-game regular season including nine Big Ten games kicking off with a Thursday night home game against Penn State.
| Date | Time | At | Opponent | Location |
| Sep 1 (Thu) | 8:00 PM | Home | Penn State | West Lafayette, Ind. (ROSS-ADE STADIUM) |
| Sep 10 (Sat) | 4:00 PM | Home | Indiana State | West Lafayette, Ind. (ROSS-ADE STADIUM) |
| Sep 17 (Sat) | 12:00 PM | Away | Syracuse | Syracuse, N.Y. |
| Sep 24 (Sat) | 7:30 PM | Home | FAU | West Lafayette, Ind. (ROSS-ADE STADIUM) |
| Oct 1 (Sat) | 12:00 PM | Away | Minnesota | Minneapolis, Minn. |
| Oct 8 (Sat) | TBA | Away | Maryland | College Park, Md. |
| Oct 15 (Sat) | TBA | Home | Nebraska | West Lafayette, Ind. (ROSS-ADE STADIUM) |
| Oct 22 (Sat) | 3:30 PM | Away | Wisconsin | Madison, Wis. |
| Nov 5 (Sat) | TBA | Home | Iowa | West Lafayette, Ind. (ROSS-ADE STADIUM) |
| Nov 12 (Sat) | TBA | Away | Illinois | Urbana-Champaign, Ill. |
| Nov 19 (Sat) | TBA | Home | Northwestern | West Lafayette, Ind. (ROSS-ADE STADIUM) |
| Nov 26 (Sat) | TBA | Away | Indiana | Bloomington, Ind. |