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.

Singles main-draw entrants Seeds Country Player Rank1 SeedTennys Sandgren931 Daniel Altmaier1062 Vasek Pospisil1133 Mitchell Krueger1484 Jack Sock1535 J. J. Wolf1596 Dmitry Popko1717Bjorn Fratangelo1728 1 Rankings are as of November 1, 2021.

Other entrants The following players received wildcards into the singles main draw: Aleksandar Kovacevic Emilio Nava Adam Walton

The following player received entry into the singles main draw using a protected ranking: Tatsuma Ito

The following players received entry into the singles main draw as alternates: Christian Harrison Malek Jaziri Peter Polansky

The following players received entry from the qualifying draw: JC Aragone Gijs Brouwer Aidan McHugh Donald Young

Champions Singles

Christopher Eubanks def. Daniel Altmaier 6–3, 6–4.

Doubles

Malek Jaziri / Blaž Rola def. Hans Hach Verdugo / Miguel Ángel Reyes-Varela 3–6, 6–3, [10–5].

References