De León, who was born 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.
He made his acting debut in the 1934 film Ang Dangal. He made eight more films as an actor before he became a director One of his unfinished projects was Juan de la Cruz (1972) with Fernando Poe, Junior.
His 1961 film The Moises Padilla Story was selected as the Philippine entry for the Best Foreign Language Film at the 32nd Academy Awards, but was not accepted as a nominee.
Gerardo de León died on July 25, 1981 at the age of 67.
De León was a medical doctor by profession, but his ultimate love for film has won him over. Nicknamed "Manong", de León is the most awarded film director in the history of the Filipino Academy of Movie Arts and Sciences" FAMAS Awards. From 1952 to 1971, he was awarded seven FAMAS Awards, three of them received consecutively. All of the films for which he won Best Director also won Best Picture at the FAMAS, namely Sawa sa Lumang Simboryo (1952), Hanggang sa Dulo ng Daigdig (1958), Huwag Mo Akong Limutin (1960), Noli Maine Tangere (1961, adapted from the novel of the same title), El Filibusterismo (1962), Daigdig ng mga Api (1965), and Lilet (1971).
