Darryl Francis was born in Wahoo, Nebraska, the son of a hotelier. He was abandoned by his parents aged thirteen. In 1917 he joined the army and served with the Nebraska National Guard in France. Returning to the US he worked in many part-time jobs while he tried to find work as a writer. He managed to find work producing movie plots, selling his first story in 1922 to William Russell and his second to Irving Thalberg. He then worked for Mack Sennett and took that experience to Warner Brothers where he wrote stories for Rin Tin Tin and under a number of pseudonyms wrote over forty scripts from 1924-29. He moved into management in 1929 and became head of production in 1931.
In 1933 he left Warners to found Twentieth Century Films with Joseph Schenck, releasing their material through United Artists. In 1935 they bought out Fox studios to become Twentieth Century-Fox. Zanuck was vice-president of this new studio and took an interventionist approach, closely involved in editing and producing. During the war he worked for the army. In the 1950s he withdrew from the studio to concentrate on independent producing in Europe. He left his wife in 1956 and the later films which he came to produce often featured his girlfriend of that day. Despite this he was largely responsible for The Longest Day (1962) being made.
He returned to control of Fox in 1962 following the studio's disastrous Cleopatra (1962), replacing Spyros Skouras. He made his son Richard head of production. He became involved in a power struggle with the board and his son from around 1969. In May 1971 Zanuck was finally forced from 'his' studio.
He died in Palm Springs, California.