- Scarlett Johansson as Black Widow / Natasha Romanoff
- Ever Anderson portrays a younger Natasha
- Florence Pugh as Yelena Belova
- Violet McGraw as Young Yelena Belova
- David Harbour as Red Guardian / Alexei Shostakov
- O-T Fagbenle as Mason
- Rachel Weisz as Melina Vostokoff
- William Hurt as Thaddeus Ross
Additionally, the Taskmaster will appear as the film's villain. Ray Winstone will portray General Dreykov, who was previously mentioned in Marvel's The Avengers. After Julia Louis-Dreyfus' debut as Valentina Allegra de Fontaine in the Disney+ series The Falcon and the Winter Soldier, it was revealed that Louis-Dreyfus was going to appear as the character in this film. Olivier Richters and Olga Kurylenko have been cast in undisclosed roles.
- This film has had multiple changes to its US release date due to the COVID-19 pandemic:
- Originally slated to be released on May 1, 2020 in the US, the release was pulled on March 17, 2020. On April 3, 2020, it was announced that the release date for this film had been pushed to November 6, 2020.
- In September 2020, the film was pushed back again to May 7, 2021.
- In March 2021, the film was pushed back for a third time to July 9, 2021, releasing in theaters and on Disney+ with Premier Access on the same day.
- This was originally intended to be the Marvel Studios property that launched Phase 4 of their cinematic universe. However, due to the film's release date delays, the Disney+ series WandaVision began Phase 4 instead. Black Widow is still slated to be the first film of Phase 4.