The 2021 Charlottesville Men's Pro Challenger was a professional tennis tournament played on indoor hard courts.

It was the twelfth edition of the tournament which was part of the 2021 ATP Challenger Tour, taking place in Charlottesville, United States from November 1 to 7, 2021.

The following players received wildcards into the singles main draw: The following player received entry into the singles main draw using a protected ranking: The following players received entry into the singles main draw as alternates: The following players received entry from the qualifying draw: