| Date: | 7–13 June |
| Edition: | 4th |
| Surface: | Hard |
| Location: | Orlando, Florida, United States |
| Champs: |  Christopher Eubanks |
| Champd: | Christian Harrison /  Peter Polansky |
| Before Name: | Orlando Open |
| Before Year: | 2021 |
| Main Name: | Orlando Open |
| After Name: | Orlando Open |
The 2021 Orlando Open II was a professional tennis tournament played on hard courts. It was the fourth edition of the tournament which was part of the 2021 ATP Challenger Tour. It took place in Orlando, Florida, United States between 7 and 13 June 2021.
| Country | Player | Rank1 | Seed | |
|---|---|---|---|---|
 Japan | Yasutaka Uchiyama | 115 | 1 | |
| Jason Jung | 160 | 2 | ||
| Jenson Brooksby | 163 | 3 | ||
 Italy | Paolo Lorenzi | 167 | 4 | |
 Ecuador | Emilio Gómez | 179 | 5 | |
| Ernesto Escobedo | 188 | 6 | ||
 Argentina | Guido Andreozzi | 200 | 7 | |
| Mitchell Krueger | 207 | 8 |
The following players received wildcards into the singles main draw:
The following players received entry from the qualifying draw:
See main article: 2021 Orlando Open II – Singles.
Christopher Eubanks def. 
Nicolás Mejía 2–6, 7–6(7–3), 6–4.See main article: 2021 Orlando Open II – Doubles.
Christian Harrison / Peter Polansky def. JC Aragone / Nicolás Barrientos 6–2, 6–3.