Schedule:
| Game | Date | Away Team (Rank) | Away Score | Home Team (Rank) | Home Score | Game Status | Result | Margin |
|---|---|---|---|---|---|---|---|---|
| 1 | 2021-09-04 | Indiana | 6 | Iowa | 34 | Final | W | 28 |
| 2 | 2021-09-11 | Iowa | 27 | Iowa State | 17 | Final | W | 10 |
| 3 | 2021-09-18 | Kent State | 7 | Iowa | 30 | Final | W | 23 |
| 4 | 2021-09-25 | Colorado State | 14 | Iowa | 24 | Final | W | 10 |
| 5 | 2021-10-01 | Iowa | 51 | Maryland | 14 | Final | W | 37 |
| 6 | 2021-10-09 | Penn State | 20 | Iowa | 23 | Final | W | 3 |
| 7 | 2021-10-16 | Purdue | 24 | Iowa | 7 | Final | L | -17 |
| 8 | 2021-10-30 | Iowa | 7 | Wisconsin | 27 | Final | L | -20 |
| 9 | 2021-11-06 | Iowa | 17 | Northwestern | 12 | Final | W | 5 |
| 10 | 2021-11-13 | Minnesota | 22 | Iowa | 27 | Final | W | 5 |
| 11 | 2021-11-20 | Illinois | 23 | Iowa | 33 | Final | W | 10 |
| 12 | 2021-11-26 | Iowa (12) | 28 | Nebraska (75) | 21 | Final | W | 7 |
| 13 | 2021-12-04 | Michigan (3) | 42 | Iowa (14) | 3 | Final | L | -39 |
| 14 | 2022-01-01 | Iowa (21) | 17 | Kentucky (24) | 20 | Final | L | -3 |