2021 Challenger de Santiago II – Singles

Sebastián Báez was the defending champion but lost in the final to Juan Pablo Varillas.

Varillas won the title after defeating Báez 6–4, 7–5 in the final.

Seeds
• # 🇦🇷 Juan Manuel Cerúndolo (first round)

• # 🇦🇷 Francisco Cerúndolo (semifinals)

• # 🇵🇪 Juan Pablo Varillas (champion)

• # 🇧🇴 Hugo Dellien (quarterfinals)

• # 🇦🇷 Sebastián Báez (final)

• # Marcelo Tomás Barrios Vera (first round)

• # 🇦🇷 Juan Ignacio Londero (first round)

• # 🇧🇷 Felipe Meligeni Alves (first round)