Lake Bell as Natasha Romanoff / Black Widow: An Avenger, highly trained former-KGB assassin, and former agent of S.H.I.E.L.D.
Florence Pugh as Yelena Belova / Black Widow: A sister to Romanoff who was trained in the Red Room as a Black Widow.
David Harbour as Alexei Shostakov / Red Guardian: The Russian super-soldier counterpart to Captain America and father-figure to Romanoff and Belova. Harbour reprises his role from previous MCU media.
O-T Fagbenle as Rick Mason: An ally from Romanoff's S.H.I.E.L.D. past who has a romantic history with her. Fagbenle reprises his role from previous MCU media.
Olga Kurylenko as Antonia Dreykov / Taskmaster: Dreykov's daughter who completes missions for the Red Room. She has photographic reflexes that allow her to mimic opponents' fighting styles, and uses techniques from superheroes such as Iron Man, Captain America, the Winter Soldier, Spider-Man, and Black Panther. Kurylenko reprises her role from previous MCU media.
Tim Roth as Emil Blonsky: The United States Secretary of State and a former Russian-born officer in the United Kingdom's Royal Marines Commandos.
Ray Winstone as Dreykov: A Russian general and the head of the Red Room. Winstone reprises his role from Black Widow (2021).
Rachel Weisz as Melina Vostokoff: A seasoned spy trained in the Red Room as a Black Widow and mother-figure to Romanoff and Belova who is now one of the Red Room's lead scientists. Weisz reprises her role from previous MCU media.
Julia Louis-Dreyfus as Contessa Valentina Allegra de Fontaine: A contessa and the director of the CIA, who is recruiting anti-heroes and former supervillains for her own team. Dreyfus reprises her role from previous MCU media.