2021 Chicago Challenger – Singles

Petra Martić was the defending champion, but chose to compete at the 2021 Western & Southern Open instead.

Clara Tauson won the title, defeating wildcard Emma Raducanu in the final, 6–1, 2–6, 6–4.

Seeds
• # 🇧🇪 Alison Van Uytvanck (first round)

• # 🇲🇪 Danka Kovinić (first round)

• # 🇺🇸 Ann Li (semifinals)

• # 🇺🇦 Anhelina Kalinina (first round)

• # 🇺🇸 Madison Brengle (first round)

• # 🇺🇸 Amanda Anisimova (second round, retired)

• # Ana Konjuh (first round)

• # 🇷🇺 Varvara Gracheva (second round)

Seeds
• # 🇸🇰 Kristína Kučová (qualifying competition)

• # 🇧🇪 Maryna Zanevska (qualified)

• # 🇫🇷 Harmony Tan (moved to main draw)

• # 🇷🇺 Vitalia Diatchenko (qualified)

Qualifiers
• # 🇬🇧 Harriet Dart

• # 🇧🇪 Maryna Zanevska

• # 🇺🇸 Caroline Dolehide

• # 🇷🇺 Vitalia Diatchenko