| Team | Line | Opponent | Date | Game Time |
|---|---|---|---|---|
| Kansas St.* | 2.0 | Nevada | 9/18/2021 | 1:05 PM |
| Cincinnati | -3.0 | Indiana* | 9/18/2021 | 11:00 AM |
| Arkansas* | -23.5 | Ga. Southern | 9/18/2021 | 3:00 PM |
| Colorado* | -1.5 | Minnesota | 9/18/2021 | 12:00 PM |
| Texas Tech* | -21.0 | FIU | 9/18/2021 | 6:00 PM |
| Georgia Tech | 28.5 | Clemson* | 9/18/2021 | 2:30 PM |
| Auburn | 6.5 | Penn St.* | 9/18/2021 | 6:30 PM |
| North Carolina* | -9.0 | Virginia | 9/18/2021 | 6:30 PM |
| Ohio | 20.0 | Louisiana* | 9/16/2021 | 7:00 PM |
| UTSA* | -13.0 | Middle Tenn. | 9/18/2021 | 5:00 PM |
| Texas A&M* | -28.0 | New Mexico | 9/18/2021 | 11:00 AM |
| Utah | -7.5 | San Diego St.* | 9/18/2021 | 6:00 PM |
| Colorado St. | 14.0 | Toledo* | 9/18/2021 | 3:00 PM |
| Purdue | 7.0 | Notre Dame* | 9/18/2021 | 1:30 PM |
| Iowa St. | -30.0 | UNLV* | 9/18/2021 | 9:30 PM |
