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.

Bianca Andreescu was the reigning champion, but withdrew before the tournament due to travel concerns caused by the ongoing COVID-19 pandemic.

Citing safety reasons, five other top-ten players (including reigning major champions Ashleigh Barty and Simona Halep) also withdrew from the event.

Williams was attempting to equal Margaret Court's all-time record of 24 major singles titles, but lost to Azarenka in the semifinals.

With Williams, Azarenka and Tsvetana Pironkova in the quarterfinals, it marked the first time in major history that three mothers did so.