Schedule:
| Game | Date | Away Team (Rank) | Away Score | Home Team (Rank) | Home Score | Game Status | Result | Margin |
|---|---|---|---|---|---|---|---|---|
| 1 | 2021-09-04 | Louisiana Tech | 34 | Mississippi State | 35 | Final | W | 1 |
| 2 | 2021-09-11 | North Carolina State | 10 | Mississippi State | 24 | Final | W | 14 |
| 3 | 2021-09-18 | Mississippi State | 29 | Memphis | 31 | Final | L | -2 |
| 4 | 2021-09-25 | LSU | 28 | Mississippi State | 25 | Final | L | -3 |
| 5 | 2021-10-02 | Mississippi State | 26 | Texas A&M | 22 | Final | W | 4 |
| 6 | 2021-10-16 | Alabama | 49 | Mississippi State | 9 | Final | L | -40 |
| 7 | 2021-10-23 | Mississippi State | 45 | Vanderbilt | 6 | Final | W | 39 |
| 8 | 2021-10-30 | Kentucky | 17 | Mississippi State | 31 | Final | W | 14 |
| 9 | 2021-11-06 | Mississippi State | 28 | Arkansas | 31 | Final | L | -3 |
| 10 | 2021-11-13 | Mississippi State | 43 | Auburn | 34 | Final | W | 9 |
| 11 | 2021-11-20 | Tennessee State | 10 | Mississippi State | 55 | Final | W | 45 |
| 12 | 2021-11-25 | Ole Miss (11) | 31 | Mississippi State (74) | 21 | Final | L | -10 |
| 13 | 2021-12-28 | Texas Tech (51) | 34 | Mississippi State (80) | 7 | Final | L | -27 |