Born in Paris, Léaud made his debut as an actor when he was 14 as Antoine Doinel, a semi-autobiographical character based on the life events of French film director François Truffaut, in The 400 Blows.
Léaud starred in four more Truffaut films depicting the life of Doinel, spanning a period of 20 years – after the short-film Antoine et Colette in 1962 - beside actress Claude Jade as his girlfriend, and then wife, Christine. Those films are: Stolen Kisses (1968), Bed & Board (1970) and Love on the Run (1979). He also collaborated with Truffaut on non-Antoine Doinel films like Two English Girls and La Nuit américaine and became the actor most commonly affiliated with him.
Léaud also acted in films by other influential directors, such as Jean-Luc Godard, Bernardo Bertolucci, Aki Kaurismaki and more recently Olivier Assayas. He appeared with Marlon Brando in the Bertolucci film Last Tango in Paris (although the two never met, since Léaud admired Brando so much that he was afraid to meet him).