- Taraji P. Henson as Katherine Goble Johnson, mathematician
- Octavia Spencer as Dorothy Vaughan, mathematician and supervisor
- Janelle Monáe as Mary Jackson, mathematician and engineer
- Kevin Costner as Al Harrison, director of the Space Task Group (STG)
- Kirsten Dunst as Vivian Mitchell, supervisor
- Jim Parsons as Paul Stafford, head engineer in STG
- Mahershala Ali as Jim Johnson, military officer who romances and eventually marries Katherine
- Aldis Hodge as Levi Jackson
- Glen Powell as John Glenn, astronaut
- Kimberly Quinn as Ruth
- Olek Krupa as Karl Zielinski, engineer (a fictionalized version of Kazimierz Czarnecki, who encourages Mary Jackson)
- Saniyya Sidney as Constance Johnson
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