Maïwenn appears for the first time on screen at the age of 5 in Next Year if All Goes Well, directed by Jean-Loup Hubert in 1981. At the age of 7, she plays the role of Isabelle Adjani as a child in Jean Becker's One Deadly Summer.
In The Elegant Criminal, she co-stars with Daniel Auteuil, as Hermine, a character whom she shares with her younger sister, Isild Le Besco. Maïwenn's first big role is that of La Gamine, opposite Johnny Hallyday in 1992. At the age of 15, she meets director Luc Besson who casts her in Leon - The Professional and The Fifth Element (1996). Maïwenn makes her return to the cinema in 2003 playing one of the heroines of Alexandre Aja's horror film, Switchblade Romance. Claude Lelouch next confides her with one of the main roles in his fresco, The Parisians (and its follow-up, The Courage to Love).
Forgive Me, the first feature film directed by Maïwenn, is released in 2006. In this scathing family portrait that resembles a French version of The Celebration, the actress-director mischievously scrambles the clues between reality and fantasy. In a vein just as personal, she pens in 2009 her second feature, All About Actresses, a humorous, offbeat reflection about actresses and the images which they convey.

Maïwenn Le Besco is also the screenwriter of "Le pois chiche" (2002).