A graduate of the prestigious IDHEC, Denis began her professional career making short films, including one with the Great Magic Circus at the Arles Festival in Provence. Other shorts were produced by Pathe for the Chronicles of France series. In 1974, she was hired as a production assistant on "Le Vieux fusil/The Hidden Gun", directed by Robert Enrico, and by 1978 was assistant director to Alain Fleischer on "Zoo-Zero". She was AD to Costa-Gavras on "Hannah K" (1983) and to indie filmmaker Jim Jarmusch on "Down By Law" (1986). It was her connection with German Wim Wenders that triggered "Chocolat". Working as Wenders' AD on "Paris, Texas" (1984), Denis thought the terrain of the American Southwest was similar to that of Cameroon, where she had spent her childhood. While working on "Wings of Desire" (1998), she began to seek financing and eventually Wenders became one of her backers.

Following the success of "Chocolat", Denis directed "Man No Run" (1989), a concert film with the Cameroon band Les Tetes Brulees. Africa was again part of Denis' motif in "S'en fout la mort/No Fear, No Die" (1990), about two Africans involved in cock fighting and again the director explored issues of racism and colonialism. She wrote and directed "J'ai pas sommeil/I Can't Sleep" (1993), a thriller which examined the intersection of seemingly unrelated, yet overlapping lives, and "U.S. Go Home" (1994), a coming of age story about teens who want to lose their virginity. In 1996, Denis scripted and helmed "Nenette et Boni", the story of a sister and a brother forging a new relationship after the death of their mother.

Denis has also worked occasionally for French TV, including "Jacques Rivette, le veilleur" (1989) and "La Robe a cerceaux" (1992). Additionally, she acted in "Mais ou et donc ornicar" (1979) and as the teen lead's mother in "En avoir (ou pas)/To Have (Or Not)" (1995).