Having listened to jazz throughout his childhood (he loved the music of Art Tatum and Charlie Parker) and attending studies at the Conservatorio Luigi Cherubini, Piero Piccioni became a musician.

Many directors sought Piero Piccioni to score the soundtracks for their films: Francesco Rosi, Mario Monicelli, Alberto Lattuada, Luigi Comencini, Luchino Visconti, Antonio Pietrangeli, Bernardo Bertolucci, Roberto Rossellini, Vittorio De Sica, Lina Wertmuller, Tinto Brass, Dino Risi, and others.

His film scores include Il bell'Antonio, Contempt, The 10th Victim, More Than a Miracle, The Deserter, The Light at the Edge of the World, Puppet on a Chain, Lucky Luciano, Camille 2000, The Nun and the Devil, Swept Away, Christ Stopped at Eboli, Fighting Back, and many Alberto Sordi movies.

The song "It's Possible" from "Il Dio Sotto la Pelle" was sampled by Hollywood JB for DJ Khaled's "Jermaine's Interlude" on his Major Key album featuring J Cole, as well as on Isaiah Rashad's Headshots (4r da Locals), and Lucki's "Waiting On".

Many other samples have been used from his vast body of work in recent years, especially from Camille 3000, Amore Mio Aiutami, Il Dio Sotto la Pelle, Anna Karenina (TV series) and Colpo Rovente, among others.

In 1953 Piccioni was falsely implicated in the Montesi scandal, after a conspiracy designed to force the resignation of his father Attilio from the highest positions in the government (he was Foreign minister at the time).