Enzo Pietropaoli was born in Genoa on September 29, 1955 and has lived in Rome since 1961. He came to the bass by a roundabout route, starting on tenor saxophone as a boy, switching to electric bass, and only then settling on the double bass that became his instrument. His professional debut came in 1975, at nineteen, in the Trio di Roma with pianist Danilo Rea and drummer Roberto Gatto, two players he has kept working with for fifty years. The trio quickly became one of Rome's standing rhythm sections for visiting Americans: it backed trombonist Curtis Fuller on a December 23, 1982 date issued by Timeless as Curtis Fuller Meets Roma Jazz Trio, and tenor saxophonist Bob Berg on Steppin' (Live in Europe), taped in Perugia on December 8, 1982 for Red Record.

The 1980s tied him to pianist Enrico Pieranunzi. Pietropaoli is the bassist on Autumn Song, recorded live at the Berlin Jazz Days on November 11, 1984 with alto saxophonist Massimo Urbani and released by Enja, and in 1986 he became a founding member of Pieranunzi's Space Jazz Trio, whose first volume was cut in Rome on June 6 and 9, 1986 for the German YVP label. That trio, with Fabrizio Sferra or Alfred Kramer at the drums, turned into the working band Paolo Piangiarelli's Philology label put behind its American guests: Chet Baker on Little Girl Blue, recorded at Recanati on March 1 and 2, 1988, Lee Konitz on Blew, taped in Rome on December 3, 1988, and Phil Woods on Phil's Mood. In parallel Pietropaoli played electric bass in Lingomania, saxophonist Maurizio Giammarco's fusion quintet with Rea, Gatto and guitarist Umberto Fiorentino, and appeared on Gatto's own Notes (1986), which featured Michael Brecker, and Ask (1987), which featured John Scofield. His first album under his own name, Orange Park, came out on Gala in 1989.

Through the 1990s he built a leader catalogue that avoided the obvious bass-trio format. To... (1992) set him against a string ensemble with Enrico Rava as guest, and its tracks were dedicated one by one to Rava, Bill Evans, Chet Baker, Charlie Haden and others. Come una volta (1996, EGEA) put him in a chamber quartet with clarinettist Gabriele Mirabassi, guitarist Battista Lena and accordionist Gianni Coscia. Stolen Songs (Splasc(H), recorded February 1994 and October 1995, released 1998) featured singer Maria Pia De Vito. He also anchored two of the decade's better-known Italian quartet records: Bella, cut with Rava, Pieranunzi and Gatto on May 29 and 30, 1990 and issued by Philology in 1994, and Shades of Chet (Via Veneto Jazz, recorded May 17 and 18, 1999), a two-trumpet Chet Baker tribute by Rava and Paolo Fresu with Stefano Bollani and Gatto.

Doctor 3, the group most responsible for his public reputation, came together in 1997 with Rea on piano and Sferra on drums. Its debut, The Tales of Doctor 3, was recorded at Rome's Millesuoni Studio on December 27 and 28, 1997 and released the following year on Via Veneto Jazz; Musica Jazz voted it the best Italian album of 1998, and the same magazine's annual Top Jazz poll named Doctor 3 the best Italian group of 1999, 2001 and 2003, while Musica&Dischi gave the follow-up The Songs Remain the Same its best-jazz-album award for 1999. The trio's method was to treat non-jazz material as raw improvising stock, moving between Pietro Mascagni and Sting, the Beatles and the Red Hot Chili Peppers, Domenico Modugno and Tom Waits, without ever announcing itself as a repertory band. It has issued ten albums to date, from Bambini Forever (2001) and the live Winter Tales, taped at Umbria Jazz in Orvieto over four nights in December 2002, to Canto Libero (2019), a programme built entirely from the Lucio Battisti and Mogol songbook.

His own projects multiplied in the 2000s and 2010s. Urban Waltz (2000) fronted a group he called the Modern Syncopators, with Mirabassi, violinist Marcello Sirignano and drummer Marcello Di Leonardo; So Right (2005, CAM Jazz) reunited him with De Vito and Rea alongside drummer Aldo Romano; Nota di Basso (2008) was a solo record for double bass and loop machine, taped in his own Rome apartment in November 2007. In 2009 the Trio di Roma reconvened for 33 on EmArcy, named for the years since its founding. The Yatra Quartet, formed in 2011 during a run of concerts in India that also supplied its name from the Sanskrit word for journey, paired him with trumpeter Fulvio Sigurtà, pianist Julian Oliver Mazzariello and drummer Alessandro Paternesi; three volumes appeared on Via Veneto Jazz in 2011, 2013 and 2015, Top Jazz voted the quartet best Italian group of 2013, and Musica Jazz named Pietropaoli instrumentalist of the year on bass in 2011. A long association with the audiophile label Fonè produced La Notte (2012), the unaccompanied Solo (recorded October 2014), the voice-and-bass duo Dos with Eleonora Bianchini, and the piano duos Easytude Live (2020) and Likewise (2022) with Mazzariello. He also runs an electric group, the Wire Trio, with pianist Enrico Zanisi and Paternesi, whose Woodstock Reloaded (2018) reworks the rock repertoire of 1969.

Alongside the jazz work Pietropaoli has been a session bassist on Italian film scores, including Paolo Sorrentino's La Grande Bellezza (2013), and has composed original soundtracks of his own: Appartamento ad Atene (2012), the debut feature of Ruggero Dipaola, for which he played double bass, guitar and percussion himself, and Te Absolvo (2016). In 2024 Arcana published Dal basso verso l'altro. Un giorno e la vita di un musicista, a book of his recollections assembled by journalist Alessandro Loppi. He remains prolific: Naked, largely electric and featuring pianist and singer Olivia Trummer with Di Leonardo, appeared on Jando Music and Via Veneto Jazz on January 19, 2024, and the SACD Gratia, a set of Marian antiphons for solo bass, followed on Fonè in 2025. Among the many sideman dates in between is Yakir Portrait (Philology, 2009), the debut of the blind Israeli pianist Yakir Arbib, where Pietropaoli and Di Leonardo form the rhythm section on tracks 3 to 6.

Pietropaoli is a supporting bassist by temperament rather than a soloist who happens to play bass, and his reputation in Italy rests on time, sound and the ability to hold a band's shape while its front line rewrites the material in real time, which is exactly what Doctor 3 and the Yatra Quartet ask of him. He plays with a large, woody, unhurried tone and a preference for long note values, and he is unusual among Italian bassists of his generation in having kept an equal footing on electric bass since the Lingomania years, a doubling he has returned to on the Wire Trio records and on Naked. Two other strands run through his work: an appetite for non-jazz source material, whether Battisti songs, Woodstock-era rock or Marian plainchant, and a taste for sparse chamber formats, which has produced solo bass albums, bass-and-voice duos, bass-and-guitar duos and the string-ensemble project To.... His Fonè recordings, made in churches and small auditoriums with valve microphones and no editing, have made him something of a reference bass sound for audiophile listeners as well as jazz ones. Musica Jazz named him instrumentalist of the year on bass in 2011, and the magazine Guitar Club had already voted him Italy's best jazz bassist three years running, from 1988 to 1990.