Mario Castelnuovo-Tedesco was born in Florence in 1895, into a prominent banking family that had existed in the city since the expulsion over the Jews from Spain in 1492. His mother introduced him to the piano while a child, and he composed his first pieces at nine years of age. Ten years later he had completed a degree in piano, and began studying under the renowned composer Ildebrando Pizzetti from whom he received a diploma in composition in 1918. At this time the blossoming artist was successful as a pianist performing as soloist, accompanist and chamber musician. The composer and pianist Alfredo Casella began including Castelnuovo-Tedesco's work in his repertoire and ensured that he was represented in the repertoires of the Societe Nazionale di Musica (later the Coporazione delle Nuove Musiche). This exposed him to a much wider European audience and he featured in the first festival of the international society of contemporary music, held in Salzburg, Austria, in 1922.

In 1926 an opera based on a play by Niccoló Machievelli, La Mandragora was premiered. Castelnuovo-Tedesco wrote many works inspired by great literature, of which this was the first. These included interpretations of works by Aeschylus, Virgil, John Keats, William Wordsworth, Walt Whitman, Frederico García Lorca, William Shakespeare, as well as the Bible and Jewish liturgy. His expression of pride in his Jewish origins, or as he described them the "splendor of past days", included his violin concerto no.2 (1931) written at the request of Jascha Heifetz.