2021 Open Città della Disfida – Singles

Gianluca Mager was the defending champion but chose not to defend his title.

Giulio Zeppieri won the title after defeating Flavio Cobolli 6–1, 3–6, 6–3 in the final.

Seeds
• # 🇸🇰 Andrej Martin (second round)

• # 🇦🇷 Juan Manuel Cerúndolo (first round, retired)

• # 🇬🇧 Jay Clarke (first round)

• # Tim van Rijthoven (second round)

• # 🇮🇹 Matteo Viola (first round)

• # 🇬🇧 Jack Draper (first round)

• # 🇮🇹 Riccardo Bonadio (first round)

• # Tseng Chun-hsin (semifinals)