2021 Knoxville Challenger

Country	Player	Rank1	Seed
USA	Tennys Sandgren	93	1
GER	Daniel Altmaier	106	2
CAN	Vasek Pospisil	113	3
USA	Mitchell Krueger	148	4
USA	Jack Sock	153	5
USA	J. J. Wolf	159	6
KAZ	Dmitry Popko	171	7
USA	Bjorn Fratangelo	172	8

• ¹ Rankings are as of November 1, 2021.^[1]

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

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

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