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| Kentucky Wildcats vs Duke Blue Devils | Tuesday, November 9, 2021 | 7:00 PM EST | Madison Square Garden in New York, NY | ESPN |
| Army Black Knights vs Duke Blue Devils | Saturday, November 13, 2021 | 7:00 PM EST | Cameron Indoor Stadium in Durham, NC | ACC Network |
| Campbell Fighting Camels vs Duke Blue Devils | Saturday, November 13, 2021 | 7:00 PM EST | Cameron Indoor Stadium in Durham, NC | ESPN+ |
| Gardner-Webb Bulldogs vs Duke Blue Devils | Tuesday, November 16, 2021 | 7:00 PM EST | Cameron Indoor Stadium in Durham, NC | ESPN+ |
| Lafayette Leopards vs Duke Blue Devils | Saturday, November 20, 2021 | 8:00 PM EST | Cameron Indoor Stadium in Durham, NC | ACC Network |
| Citadel Bulldogs vs Duke Blue Devils | Tuesday, November 23, 2021 | 9:00 PM EST | Cameron Indoor Stadium in Durham, NC | ACC Network |
| Duke Blue Devils vs Gonzaga Bulldogs | Saturday, November 27, 2021 | 10:30 PM EST | T-Mobile Arena in Las Vegas, NV | ESPN |
| Duke Blue Devils vs Ohio State Buckeyes | Wednesday, December 1, 2021 | 9:30 PM EST | Value City Arena in Columbus, OH | ESPN |
| South Carolina State Bulldogs vs Duke Blue Devils | Wednesday, December 15, 2021 | 8:00 PM EST | Cameron Indoor Stadium in Durham, NC | ACC Network |
| Cleveland State Vikings vs Duke Blue Devils | Saturday, December 18, 2021 | 4:00 PM EST | Cameron Indoor Stadium in Durham, NC | ACC Network |
| Virginia Tech Hokies vs Duke Blue Devils | Thursday, December 23, 2021 | 9:00 PM EST | Cameron Indoor Stadium in Durham, NC | ESPN2 |
| Duke Blue Devils vs Clemson Tigers | Thursday, December 30, 2021 | 7:00 PM EST | Littlejohn Coliseum in Clemson, SC | ACC Network |
| Georgia Tech Yellow Jackets vs Duke Blue Devils | Wednesday, January 5, 2022 | 9:00 PM EST | Cameron Indoor Stadium in Durham, NC | ACC Network |
| Miami Hurricanes vs Duke Blue Devils | Sunday, January 9, 2022 | 8:00 PM EST | Cameron Indoor Stadium in Durham, NC | ACC Network |
| Duke Blue Devils vs Wake Forest Demon Deacons | Thursday, January 13, 2022 | 7:00 PM EST | Lawrence Joel Veterans Memorial Coliseum in Winston-Salem, NC | ACC Network |
| NC State Wolfpack vs Duke Blue Devils | Saturday, January 15, 2022 | 2:00 PM EST | Cameron Indoor Stadium in Durham, NC | ESPN+ |
| Duke Blue Devils vs Florida State Seminoles | Tuesday, January 18, 2022 | 9:00 PM EST | Donald L. Tucker Center in Tallahassee, FL | ESPN |
| Syracuse Orange vs Duke Blue Devils | Saturday, January 22, 2022 | 12:00 PM EST | Cameron Indoor Stadium in Durham, NC | ESPN+ |
| Clemson Tigers vs Duke Blue Devils | Wednesday, January 26, 2022 | 7:00 PM EST | Cameron Indoor Stadium in Durham, NC | ESPN+ |
| Duke Blue Devils vs North Carolina Tar Heels | Saturday, February 5, 2022 | 6:00 PM EST | Dean E. Smith Center in Chapel Hill, NC | ESPN |
| Virginia Cavaliers vs Duke Blue Devils | Tuesday, February 8, 2022 | 7:00 PM EST | Cameron Indoor Stadium in Durham, NC | ESPN |
| Duke Blue Devils vs Boston College Eagles | Saturday, February 12, 2022 | 5:00 PM EST | Silvio O. Conte Forum in Chestnut Hill, MA | ACC Network |
| Wake Forest Demon Deacons vs Duke Blue Devils | Wednesday, February 16, 2022 | 7:00 PM EST | Cameron Indoor Stadium in Durham, NC | ESPN+ |
| Florida State Seminoles vs Duke Blue Devils | Saturday, February 19, 2022 | 6:00 PM EST | Cameron Indoor Stadium in Durham, NC | ESPN |
| Duke Blue Devils vs Virginia Cavaliers | Thursday, February 24, 2022 | 7:00 PM EST | John Paul Jones Arena in Charlottesville, VA | ESPN |
| Duke Blue Devils vs Syracuse Orange | Saturday, February 26, 2022 | 6:00 PM EST | Carrier Dome in Syracuse, NY | ESPN |
| Duke Blue Devils vs Pittsburgh Panthers | Wednesday, March 2, 2022 | 8:00 PM EST | Petersen Events Center in Pittsburgh, PA | ACC Network |
