Ardant grew up in Monaco until age 17 when she moved to Aix-en-Provence to attend university. In her early twenties her interest turned to acting and in 1974 she made her first appearance on stage.

By the early 1980s she was a major motion picture star, gaining international recognition for her role opposite Gérard Depardieu in La Femme d'à côté (The Woman Next Door). The film, directed by François Truffaut, brought Ardant her first Cesar Award nomination for best actress in 1982 and in 1984 she was nominated again for Vivement dimanche! Eventually she became Truffaut's companion, giving birth to their daughter, Joséphine Truffaut, on September 28, 1983.

Initially, her youthful beauty brought popularity but over time her sophistication and acting skills have made her one of France's most admired actresses. She proved her versatility, playing a comedic role in Pédale douce for which she won the 1997 Cesar Award for Best Actress.

Fluent in English, Ardant has starred in several Hollywood and British films. Her most recent English-language film was the Franco Zeffirelli production Callas Forever, in which she portrayed opera diva Maria Callas. It opened the 14th Annual Palm Springs International Film Festival on January 9, 2003.

Ardant has appeared in more than fifty motion pictures.