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* {{flagicon|CHN}} ]<ref name="US Open Withdrawals"/> → replaced by {{flagicon|AUS}} ]{{efn|] was the next player initially entered into the main draw, but she later withdrew due to a hip injury.<ref>{{cite web|url=https://www.smh.com.au/sport/tennis/untimely-hip-injury-stops-priscilla-hon-heading-to-the-united-states-20200824-p55osf.html|title=Untimely hip injury stops Hon heading to the United States|website=www.smh.com.au}}</ref>}}{{efn|After Hon's withdrawal from the event, ] was the next player initially entered into the main draw, but withdrew citing injury setbacks.}}
* {{flagicon|CHN}} ]<ref name="US Open Withdrawals"/> → replaced by {{flagicon|AUS}} ]{{efn|] was the next player initially entered into the main draw, but she later withdrew due to a hip injury.<ref>{{cite web|url=https://www.smh.com.au/sport/tennis/untimely-hip-injury-stops-priscilla-hon-heading-to-the-united-states-20200824-p55osf.html|title=Untimely hip injury stops Hon heading to the United States|website=www.smh.com.au}}</ref>}}{{efn|After Hon's withdrawal from the event, ] was the next player initially entered into the main draw, but withdrew citing injury setbacks.}}
Naomi Osaka defeated Victoria Azarenka in the final, 1–6, 6–3, 6–3, to win the Women's Singles tennis title at the 2020 US Open. This was Osaka's second US Open title and third major overall. She was the first player to win the US Open women's singles title after losing the first set since Arantxa Sánchez Vicario won the title in 1994.
Osaka became the first player from a fully Asian country to win a third Grand Slam singles title, the first player since Jennifer Capriati to win 3 such titles in 3 attempts and, at 22 years of age, the youngest player to win those 3 titles since Maria Sharapova won the 2008 Australian Open. Azarenka, who participated in her first Grand Slam tournament final since the 2013 US Open, was aiming to become the first mother to win a Grand Slam singles title since Kim Clijsters won the 2011 Australian Open.
Bianca Andreescu was the defending champion, but she withdrew before the tournament began due to travel concerns related to the ongoing COVID-19 pandemic. Citing safety reasons, 5 other top 10 players (including reigning Grand Slam champions Ashleigh Barty and Simona Halep) also withdrew from the event as well. In all, 24 players ranked inside the top 100 were absent from the tournament. The absences of Barty and Halep, respectively world No. 1 and 2, made this the first Grand Slam event since the 2004 Wimbledon Championships, when both Justine Henin-Hardenne and Clijsters withdrew prior to the event, that neither of the top 2 ranked players in the world were present in the draw.
There were no qualifiers this year. The WTA rankings valid on August 3 (being the rankings from March 16) were used to determine the main-draw entry list.
With her first round win over Kristie Ahn, Serena Williams surpassed Chris Evert for the most match wins (102) in US Open history. Williams was attempting to equal Margaret Court's all-time record of 24 Grand Slam singles titles and was also trying to set a new Open Era record by winning a seventh US Open singles title, but lost to Azarenka in the semifinals. Despite her loss, this made Williams the first player in history to reach the semifinals of a Grand Slam, as well as the US Open, in 4 decades: the 1990s, 2000s, 2010s and 2020s.
29 of the 32 seeded women progressed to the second round; the most since the US Open changed from 16 seeds to 32 seeds in 2001.
With Williams, Azarenka and Tsvetana Pironkova all winning their fourth round matches, it marked the first time in Grand Slam history that 3 mothers had reached the quarterfinals. The semifinal between Williams and Azarenka was the first semifinal between 2 mothers in Grand Slam history.
This was Kim Clijsters' first Grand Slam appearance since the 2012 US Open, following a second retirement from tennis and comeback to the sport in February 2020. Clijsters was awarded a wildcard into the main draw, but she lost to Ekaterina Alexandrova in three sets.
This was the first time since the 1980 US Open that both semifinals and the final went to 3 sets.
Naomi Osaka
Victoria Azarenka
Karolína Plíšková (Second round)
Sofia Kenin (Fourth round)
Petra Martić (Fourth round)
Johanna Konta (Second round)
Garbiñe Muguruza (Second round)
Elena Rybakina (Second round)
Anett Kontaveit (Fourth round)
Maria Sakkari (Fourth round)
Elise Mertens (Quarterfinals)
Angelique Kerber (Fourth round)
Dayana Yastremska (Second round)
Ekaterina Alexandrova (Second round)
Magda Linette (Third round)
Zhang Shuai (First round)
Ons Jabeur (Third round)
Kristina Mladenovic (Second round)
Anastasija Sevastova (Second round)
Rebecca Peterson (First round)
Tsvetana Pironkova
J Paolini
A Tomljanović
A Rus
V Golubic
D Kovinić
K Juvan
I-C Begu
T Babos
M Puig
B Haas
N Stojanović
V Kužmová
LA Fernandez
Hsieh Su-wei → replaced by