After graduating from the Conservatoire de la rue Blanche in 1954 with two First Prizes in Modern and Classical Comedy, Girardot joined the Comédie Française, where she was a resident actor from 1954 to 1957.
[citation needed] Her performance in a revival of Jean Cocteau's play La Machine à écrire in 1956 was lauded by the author who called her "The finest dramatic temperament of the Postwar period".
Travelling back and forth between France and Italy, Girardot worked with Italian directors such as Marco Ferreri, appearing in three of his films, including the controversial The Ape Woman (1964) and Dillinger Is Dead (1968).
In 1972, she said in an interview to The New York Times, citing as Exhibit A her role as a sideshow freak in The Ape Woman, "I think I've proven that I'm opposed to typecasting.
Girardot became one of the symbols of the 1970s feminist movement in France, as the audience embraced the "everywoman" quality she brought to the strong-minded female characters she regularly played in both dramas and comedies.
[citation needed] In her 1989 autobiography, Vivre d'aimer, she wrote: "People didn't come to watch a beautiful, vamp-like creature, but simply a woman.
However, Girardot had a major comeback on the big screen playing a peasant wife in Claude Lelouch's Les Misérables (1995).
Girardot is the highest ranked woman in the list of French stars who have appeared in the most movies that have attracted more than one million admissions in France since 1945, with 44 films.
After going public in the 21 September 2006 issue of Paris Match with the news that she was suffering from Alzheimer's disease, she became a symbol of the illness in France.