See main article: 2021 Challenger de Santiago III.
Diego Hidalgo and Nicolás Jarry were the defending champions[1] but only Hidalgo chose to defend his title, partnering Sergio Galdós. Hidalgo lost in the quarterfinals to Hans Hach Verdugo and Miguel Ángel Reyes-Varela.
Evan King and Max Schnur won the title after defeating Hach Verdugo and Reyes-Varela 3–6, 7–6(7–3), [16–14] in the final.