He was born Francesco Sparanero in San Prospero, Parma, Italy, and grew up in Bedonia and in Milan. He studied briefly at the Facoltà di Economia e Commercio before leaving to study at the Piccolo Teatro di Milano.

His first film role was a small part in La Ragazza in Prestito (1964), he had his first lead role in Sergio Corbucci's Django (1966) a Spaghetti Western and one of his most well-known films. In 1966 from Django he went on to appear in eight more films released that year including Texas, Addio and Tempo di Massacro. In 1967 he appeared in his first English language film, Camelot as Lancelot, where he met his future romantic partner, Vanessa Redgrave. A certain lack of facility with English tended to limit these roles, although he also appeared in other English language films including The Virgin and the Gypsy (1970), Force 10 From Navarone (1978), Enter the Ninja (1981) and Die Hard 2 (1990). Although often typecast in films like Los amigos (1972) or Keoma (1976) he has attempted an impressive range of characters, like Abel in John Huston's epic The Bible: In The Beginning (1966), the humiliated engineer out for revenge in Street Law, and the gay lieutenant in Querelle (1982). He has appeared in almost 150 films, and has written, produced and starred in one - Jonathan degli orsi (1993).

More recently, he starred in Hungarian director Gábor Koltay's Honfoglalás (Conquest) in 1996, and subsequently in Koltay's Sacra Corona (Holy Crown) in 2001.

He was romantically involved with British actress Vanessa Redgrave, and in 1969 they had a son, Carlo Gabriel Sparanero (known professionally as Carlo Nero), a screen-writer and director.