De León, who was born as Gerardo Ilagan, was a member of the Ilagan clan of Philippine motion pictures, which includes Robert Arevalo, Conrado Conde, Angel Esmeralda, Eddie Ilagan, Ronaldo Valdez, musical scorer Tito Arévalo, and his daughter Liberty Ilagan. De León was a medical doctor by profession, but his ultimate love for film has won him over. He made eight more films as an actor before he became a director. He made his directorial debut in 1939's Bahay-Kubo, starring Fely Vallejo (who he later married). One of his unfinished projects was in the late Fernando Poe, Jr.'s Juan de la Cruz in 1972.
All of the films for which he won Best Director also won Best Picture at the FAMAS: Sawa sa Lumang Simboryo (1952), Hanggang sa Dulo ng Daigdig (1958), Huwag Mo Akong Limutin (1960), Noli Me Tangere (1961, adaptation of the novel Noli Me Tangere ), El Filibusterismo (1962), Daigdig ng mga Api (1965), Lilet (1971).