Born into poverty in Sora (Frosinone), he began his career as a theatre actor in the early 1920s and joined Tatiana Pavlova's theatre company in 1923.
In 1933 he founded his own company with his wife Giuditta Rissone and Sergio Tofano. The company performed mostly light comedies, but they also staged plays by Beaumarchais, and worked with famous directors like Luchino Visconti.
His meeting with Cesare Zavattini was a very important event: they wrote together some of the most celebrated films of the neorealistic age, like SciusciÓ (Shoeshine) and Ladri di biciclette (The Bicycle Thief).
One of his best-received is La Ciociara (Two Women) (1961): Sophia Loren won the Oscar for her performance, and critics widely regard the film a classic. De Sica died in Paris on November 13, 1974.