| Date | Time | At | Opponent | Location | TV | Result |
| Sept. 3, 2021 (Friday) | 6:00 PM | Away | Virginia Tech | Blacksburg, VA | ESPN | 17-10 L |
| Sept. 11, 2021 (Saturday) | 7:30 PM | Home | Georgia State | Chapel Hill | RSN | 59-17 W |
| Sept. 18, 2021 (Saturday) | 7:30 PM | Home | Virginia | Chapel Hill | ACC Network | 59-39 W |
| Sept. 25, 2021 (Saturday) | 7:30 PM | Away | Georgia Tech | Atlanta, Ga. (Mercedes-Benz Stadium) | ACC Network | 45-22 L |
| Oct. 2, 2021 (Saturday) | 12 Noon | Home | Duke | Chapel Hill | ESPN 2 | 38-7 W |
| Oct. 9, 2021 (Saturday) | 3:30 PM | Home | Florida State | Chapel Hill | ESPN | 35-25 L |
| Oct. 16, 2021 (Saturday) | 3:30 PM | Home | Miami | Chapel Hill | ACC Network | 45-42 W |
| Oct. 30, 2021 (Saturday) | 7:30 PM | Away | Notre Dame | South Bend, Ind. | NBC | 44-34 L |
| Nov. 6, 2021 (Saturday) | 12 Noon | Home | Wake Forest | Chapel Hill | ABC | 58-55 W |
| Nov. 11, 2021 (Thursday) | 7:30 PM | Away | Pittsburgh | Pittsburgh, PA | ESPN | 30-23/OT L |
| Nov. 20, 2021 (Saturday) | 12 Noon | Home | Wofford | Chapel Hill | RSN/ESPN3 | 34-14 W |
| Nov. 26, 2021 (Friday) | 7 PM | Away | NC State | Raleigh, N.C. | ESPN | 34-30 L |
“There’s a whole season left to play” LOL