| 9/4/2021 | Louisiana Tech (3-9) | 34 | at | Mississippi State | 35 | CUSA | ||
| 9/11/2021 | North Carolina State (9-3) | 10 | at | Mississippi State | 24 | ACC | ||
| 9/18/2021 | Mississippi State | 29 | at | Memphis (6-6) | 31 | at AAC | ||
| 9/25/2021 | LSU (6-7,3-5) | 28 | at | Mississippi State | 25 | |||
| 10/2/2021 | Mississippi State | 26 | at | Texas A&M (8-4,4-4) | 22 | |||
| 10/16/2021 | Alabama (13-2,8-2) | 49 | at | Mississippi State | 9 | |||
| 10/23/2021 | Mississippi State | 45 | at | Vanderbilt (2-10,0-8) | 6 | |||
| 10/30/2021 | Kentucky (10-3,5-3) | 17 | at | Mississippi State | 31 | |||
| 11/6/2021 | Mississippi State | 28 | at | Arkansas (9-4,4-4) | 31 | |||
| 11/13/2021 | Mississippi State | 43 | at | Auburn (6-7,3-5) | 34 | |||
| 11/20/2021 | Tennessee State (5-6) | 10 | at | Mississippi State | 55 | OVC (1AA) | ||
| 11/25/2021 | Mississippi (10-3,6-2) | 31 | at | Mississippi State | 21 | |||
| 12/28/2021 | Mississippi State | 7 | vs | Texas Tech (7-6) | 34 | Liberty Bowl - Memphis TN | vs B12 |
| vs Mississippi State | vs Other Opponents | Mississippi State compared to OOs | |
| Record: | 6-7 | 88-63 | |
| Points Scored: | 25.92 | 29.67 | 3.75 |
| Points Allowed: | 29.08 | 24.89 | 4.19 |
| Margin: | -3.16 | 4.78 | 7.94 |
| Total Points: | 55.00 | 54.56 | 0.44 |