| 2021 Knoxville Challenger | |
|---|---|
| Date | 8–14 November |
| Edition | 17th |
| Surface | Hard (Indoor) |
| Location | Knoxville, United States |
| Champions | |
| Singles | |
 Christopher Eubanks | |
| Doubles | |
 Malek Jaziri /  Blaž Rola | |
The 2021 Knoxville Challenger was a professional tennis tournament played on indoor hard courts. It was the seventeenth edition of the tournament which was part of the 2021 ATP Challenger Tour. It took place in Knoxville, United States between 8 and 14 November 2021.