- Jessica Chastain as Mason "Mace" Brown - A CIA agent who goes off the record to recruit a team to discover and put a stop to an international terrorist group. Brown believes that this group owns (or is about to own) a very powerful and lethal weapon that could end the world.
- Lupita Nyong'o as Khadijah - A former MI6 agent. A no-nonsense, straight-talking woman, Khadijah is the world's best computer specialist according to Brown and her cutting-edge tech skills can help Brown achieve her mission.
- Diane Kruger as Marie Schmidt - A rival BND (Federal Intelligence Service Germany) agent who knows her guns and is exceptionally good at them. She eventually teams up with Brown on the mission.
- Penelope Cruz as Graciela - A skilled psychologist who works with the DNI, the Colombian intelligence agency. A skilled agent and psychologist, Graciela is not like her fellow agents. She is a mother of two and is not trained for the field but Brown and her team are going to make sure Graciela catches up.
- Fan Bingbing as Lin Mi Sheng - a mysterious Chinese MSS agent who is constantly tracking Brown and her team's every move. Eventually, she also joins forces with them to thwart their common enemy.