She is known for her roles in the American television series Ramy (2019–present) as Dena Hassan, and Moon Knight (2022) as Layla El-Faouly / Scarlet Scarab, the first Arab and first Egyptian character and superhero in the Marvel Cinematic Universe.

[5][12] Calamawy completed high school in Bahrain,[2] and at 17 she moved to Boston, Massachusetts, to study industrial design,[13] because her father wanted her to.

[18] In 2022, Calamawy starred in the Disney+ miniseries Moon Knight, based on the Marvel Comics featuring the character of the same name,[18][19] where she portrayed Layla El-Faouly, an Egyptian archeologist and estranged wife of Marc Spector (portrayed by Oscar Isaac),[20] who later becomes the Scarlet Scarab, the first Arab and first Egyptian character and superhero in the Marvel Cinematic Universe.

[21][22] In July 2022, she joined the voice cast of the animated television series Moon Girl and Devil Dinosaur as a guest star.

[26][27] In October 2022, Calamawy joined the cast of Duke Johnson's upcoming thriller, The Actor,[28][29] in which she plays five different characters.

[11][5] In October 2023, she signed an open letter for the Artists4Ceasefire campaign calling for a ceasefire in the Gaza Strip during the Israel-Hamas war.