| Date: | August 16–22 |
| Edition: | 2nd |
| Draw: | 32S / 16D |
| Surface: | Hard, outdoor |
| Prize Money: | $125,000 |
| Category: | WTA 125K series |
| Location: | Chicago, United States |
| Venue: | XS Tennis Village |
| Champs: | Clara Tauson |
| Champd: |  Eri Hozumi /  Peangtarn Plipuech |
| Before Name: | Oracle Challenger Series – Chicago |
| Before Year: | 2018 |
| After Year: | 2023 |
| Main Name: | Oracle Challenger Series – Chicago Chicago Challenger |
The 2021 Chicago Challenger was a professional tennis tournament played on outdoor hard courts. It was part of the 2021 WTA 125K series. It was the second edition of the tournament which took place from August 16 to 22, 2021 in Chicago, United States.[1]
See main article: article and 2021 Chicago Challenger – Singles.
Emma Raducanu, 6–1, 2–6, 6–4[2]See main article: article and 2021 Chicago Challenger – Doubles.
Eri Hozumi / Peangtarn Plipuech def. Mona Barthel / Hsieh Yu-chieh, 7–5, 6–2| Country | Player | Rank1 | Seed | |
|---|---|---|---|---|
 Belgium | Alison Van Uytvanck | 60 | 1 | |
 Montenegro | Danka Kovinić | 66 | 2 | |
 United States | Ann Li | 69 | 3 | |
 Ukraine | Anhelina Kalinina | 78 | 4 | |
| United States | Madison Brengle | 79 | 5 | |
| United States | Amanda Anisimova | 86 | 6 | |
| Ana Konjuh | 88 | 7 | ||
 Russian Federation | Varvara Gracheva | 89 | 8 |
The following players received wildcards into the singles main draw:
The following players received entry using protected rankings:
The following players received entry from the qualifying draw:
Harmony Tan Nao Hibino → replaced by Ana Konjuh
Kaia Kanepi → replaced by Anna Kalinskaya Marta Kostyuk → replaced by 
Nuria Párrizas Díaz Anastasia Potapova → replaced by Jule Niemeier
Nina Stojanović → replaced by Greet Minnen| Country | Player | Country | Player | Rank1 | Seed | |
|---|---|---|---|---|---|---|
| United States | Kaitlyn Christian | Lesley Pattinama Kerkhove | 152 | 1 | ||
| Julia Lohoff |  Czech Republic | Renata Voráčová | 170 | 2 | ||
| United Kingdom | Harriet Dart | United States | Caroline Dolehide | 180 | 3 | |
 Italy | Sara Errani |  Georgia | Oksana Kalashnikova | 202 | 4 |
The following pair received a wildcard into the doubles main draw:
The following pairs received entry into the doubles main draw using protected rankings:
Eri Hozumi / Valeria Savinykh → replaced by Eri Hozumi / Peangtarn Plipuech