The 2022 San Luis Open Challenger was a professional tennis tournament played on clay courts. It was the 27th edition of the tournament which was part of the 2022 ATP Challenger Tour. It took place in San Luis Potosí, Mexico between 11 and 17 April 2022.
| Country | Player | Rank1 | Seed | |
|---|---|---|---|---|
 Slovakia | Andrej Martin | 129 | 1 | |
| Nicolás Jarry | 139 | 2 | ||
 United States | Ernesto Escobedo | 142 | 3 | |
 Argentina | Facundo Mena | 159 | 4 | |
 United Kingdom | Jay Clarke | 166 | 5 | |
| Marc-Andrea Hüsler | 176 | 6 | ||
 Italy | Federico Gaio | 186 | 7 | |
| Argentina | Renzo Olivo | 203 | 8 |
The following players received wildcards into the singles main draw:
The following players received entry into the singles main draw as alternates:
The following players received entry from the qualifying draw:
Gilbert Klier Júnior
Roberto Quiroz
Shang Juncheng Matías ZukasSee main article: 2022 San Luis Open Challenger – Singles.
Renzo Olivo 6–7(2–7), 6–4, 7–5.See main article: 2022 San Luis Open Challenger – Doubles.
Nicolás Barrientos / 
Miguel Ángel Reyes-Varela def. 
Luis David Martínez / Felipe Meligeni Alves 7–6(13–11), 6–2.
