He was born in Rome and was educated at the Conservatory of Santa Cecilia in the trumpet, composition and Choral music and Choral direction. He began writing music for films in 1955 but continued to work in classical composition and arrangement. In 1956 he married Maria Travia. In 1964 he began his famous collaboration with Sergio Leone and also Bernardo Bertolucci. For Leone he wrote the score for Per un Pugno di Dollari in 1965 and continued with a number of other Spaghetti Westerns. By 1968 he was reducing his work outside of film, in the same year he wrote twenty scores for films.
He received his first Nastro d'Argento in 1970 for the music in Metti, una Sera a Cena and his second only a year later for Sacco and Vanzetti. He received his first nomination for an Academy Award in 1979 for the score to Days of Heaven and another in 1986 for The Mission, 1987 for The Untouchables and 2001 for Malèna.
Morricone's film music has been recorded by other artists on a number of occasions: Hugo Montenegro had a hit with a version of the theme from The Good, the Bad and the Ugly in both the UK and the US and followed it up with an album of Morricone's music in 1968, and John Zorn recorded an album of Morricone's music, The Big Gundown, in the mid-1980s.