2021 Challenger de Santiago III – Singles

Juan Pablo Varillas was the defending champion but lost in the quarterfinals to Marcelo Tomás Barrios Vera.

Sebastián Báez won the title after defeating Felipe Meligeni Alves 3–6, 7–6(8–6), 6–1 in the final.

Seeds
• # 🇦🇷 Juan Manuel Cerúndolo (quarterfinals)

• # 🇦🇷 Francisco Cerúndolo (quarterfinals)

• # 🇵🇪 Juan Pablo Varillas (quarterfinals)

• # 🇧🇷 Thiago Seyboth Wild (first round)

• # 🇦🇷 Sebastián Báez (champion)

• # Marcelo Tomás Barrios Vera (semifinals)

• # 🇦🇷 Juan Ignacio Londero (second round)

• # 🇫🇷 Enzo Couacaud (first round)