The 2021 Columbus Challenger was a professional challenger level tennis tournament played on indoor hard courts.

It was the tenth edition of the men's tournament which was part of the 2021 ATP Challenger Tour[1] and the first edition of the women's event, that was part of 2021 WTA 125K series.

[2] It took place in Columbus, United States between 20 and 26 September 2021.

The following players received entry into the singles main draw as wildcards: The following players received entry into the singles main draw as alternates: The following players received entry into the singles main draw from the qualifying draw: The following players received entry as lucky losers: The following players received entry into the singles main draw as wildcards: The following player was accepted directly into the main draw using a protected or a special ranking: The following players received entry into the singles main draw from the qualifying draw: The following player received entry into the singles main draw as a lucky loser: The following pairs received wildcards into the doubles main draw: