De Filippo was born in Naples to playwright Eduardo Scarpetta and theatre seamstress and costumier Luisa De Filippo. He began acting at the age of five and in 1932 formed a theater company with his brother Peppino and sister Titina. Peppino left the troupe in 1944 and Titina departed by the early 1950s. De Filippo starred in De Sica's L'oro di Napoli with Totò and Sophia Loren in 1954. His translation of Shakespeare's The Tempest into Neapolitan was published in 1982.

In 1981, De Filippo was appointed life senator of the Italian Republic. He died four years later in Rome. His artistic legacy has been carried over by his son.

Theatre

• Farmacia di turno (The All-night Chemist, 1920)
• Uomo e galantuomo (Man and Gentleman, 1922)
• *Requie a l'anema soja/I morti non fanno paura (May his soul rest, 1926)
• Ditegli sempre di sì (Always tell him "yes", 1927)
• Filosoficamente (Philosophically, 1928)
• Sik-sik, l'artefice magico (Sik-sik the magical maker, 1929)
• Chi è cchiu' felice 'e me (Who's Happier than Me?, 1929)
• Quei figuri di trent'anni fa (Those Dudes of 30 Years Ago, 1929)
• Ogni anno punto e da capo (Every Year Back from the Start, 1931)
• È arrivato 'o trentuno (The 31st is Here, 1931)
• Natale in casa Cupiello (Christmas at the Cupiello's, 1931)
• La voce del padrone/Il successo del giorno (Success of the Day, 1932)
• Napoli milionaria (The Millions of Naples, 1945)
• Filumena Marturano (1946)
• Questi fantasmi (These Ghosts, 1946)
• Le voci di dentro (Inner Voices, 1948)
• Mia famiglia (Family of Mine, 1955)
• Bene mio e core mio (My Heart, my Treasure, 1955)
• De Pretore Vincenzo (Vincent De Pretore, 1957)
• Sabato, domenica e lunedì (Saturday, Sunday and Monday ,1959)
• Il sindaco del rione Sanità (Mayor of "Sanità" alley, 1961)
• Il monumento (The Monument, 1970)
• Gli esami non finiscono mai (Exams never end ,1973)

Filmography

• In campagna e' caduta una stella (A Star Fell in the Country, 1939)
• Non ti pago! (1942)
• Ti conosco, mascherina! (I know you, little Mask!, 1943—1944)
• Napoli milionaria (The Millions of Naples, 1950)
• Filumena Marturano (1951)
• I sette peccati capitali ( Seven Deadly Sins, 1952)
• Marito e moglie (Man and Wife, 1952)
• Ragazze da marito (Girls to be married, 1952)
• It Happened in the Park (1953)
• Napoletani a Milano (Neapolitans in Milan, 1953)
• Questi fantasmi (These Ghosts, 1954)
• Fortunella (Happy-go-lucky Girl, 1958)
• Il sogno di una notte di mezza sbornia (A Midsummer's Hangover Dream, 1959)
• Ferdinando I, re di Napoli (1959)
• Ghosts of Rome (1961)
• Oggi, domani, dopodomani (Today, Tomorrow and the Day After, 1965)
• Spara più forte, più forte... non capisco(Shoot louder, I can't hear You, 1966)
• Ghosts - Italian Style (1968)