Fabio Zeppetella was born in 1961 in Terracina, on the coast between Rome and Naples, and moved to Rome as a young man to join the city's jazz scene during what Musica Jazz describes as its second flourishing. He has been a working professional since 1982. Rome in those years leaned toward bebop and acoustic playing rather than free jazz or electric experiment, and Zeppetella's early concerts took place at clubs such as the Music Inn and the Saint Louis, among contemporaries that included Roberto Gatto, bassist Francesco Puglisi and Rita Marcotulli.

His first recorded credits on Discogs come from the Roman studio and band circuit of the 1980s. He plays guitar on Wilfred Percussion (1983), a Latin-jazz and soul session with Cicci Santucci on trumpet, and electric guitar on City Sound (1987), by the later Area line-up built around drummer Giulio Capiozzo. He also spent years in pianist Riccardo Fassi's Tankio Band, a Roman big band, appearing on Il Principe (1989, with saxophonist Steve Grossman as featured soloist), Notte (1991) and Plays the Music of Frank Zappa (1995). Those records put him beside trumpeters Aldo Bassi and Claudio Corvini, bassist Massimo Moriconi, and guests Flavio Boltro and Antonello Salis.

The Discogs record of his own leadership begins with Moving Lines (1995), a quartet album with the British trumpeter Kenny Wheeler as featured guest, bassist Ares Tavolazzi and drummer Fabrizio Sferra. It was recorded on January 30 and 31, 1995; Zeppetella wrote five of the seven pieces and Tavolazzi the other two. The 1990s also brought A Tribute to Wes Montgomery (Philology, 1998), an organ trio with Emmanuel Bex and Roberto Gatto in the format Montgomery himself favored, and Greetings From..., recorded in April 1997 with trumpeter Paolo Fresu, drummer Pier Paolo Pozzi and French bassist Jean-Jacques Avenel and issued in 1999. Between those dates he played guitar on Gatto's 7# (RCA Victor, 1997), alongside Javier Girotto and bassist Dario Deidda, and Deidda and drummer Ettore Fioravanti were his rhythm section on Fioravanti's Canzoni Non Cantate (1993). A biography published by the Ancona Jazz festival adds that he won a European jazz guitar competition run by the Orchestre National de Jazz in Paris in 2000.

The 2000s widened the catalog. Temi Variazioni & Metamorfosi (Picanto, 2007) began a long partnership with guitarist Umberto Fiorentino. The Auditorium Session was recorded on April 13, 2005 at Rome's Auditorium Parco della Musica and released in 2008: it is billed to American trumpeter Tom Harrell, saxophonist Maurizio Giammarco, Zeppetella, Deidda and Sferra. Jobim Variations (EmArcy, 2009), recorded November 13 to 15, 2008, is an acoustic-guitar reading of Antonio Carlos Jobim with pianist Danilo Rea, Tavolazzi and drummer Aldo Romano. No Clue (Brave Art, 2010) reunited him with Bex and Gatto, and in 2012 he was among the artists on Universal's three-disc compilation The Italian Jazz Job.

In 2013 he made Handmade for Via Veneto Jazz with an American rhythm section, pianist Aaron Goldberg, bassist Matt Penman and drummer Gregory Hutchinson, billed as the Fabio Zeppetella American Quartet. It is built on his own compositions plus John Coltrane's "Moment's Notice," played as a street samba, and includes an acoustic-guitar ballad, "Via Manzoni 7." Chansons! (Via Veneto Jazz, 2017) paired him again with Bex and Gatto and added alto saxophonist Géraldine Laurent for a program of Italian and French songs: six by Italian writers including Bruno Martino, Fabrizio De André, Francesco De Gregori and Pino Daniele, and five French pieces including Jacques Brel, Léo Ferré, Yves Montand and Joe Dassin. Wordless Song (Emme, released December 24, 2019) is a second album of guitar duets with Umberto Fiorentino, recorded at Tube Recording Studio in Fara in Sabina, mixing acoustic archtop guitars with baritone guitar, loops and guitar synthesizer. He followed it with Stones (Emme, 2021), a trio with clarinetist Gabriele Mirabassi and Deidda.

Jazz Masters (Jando Music, 2023) documents the working quartet he says he has kept with Tavolazzi, drummer Fabrizio Sferra and pianist Dado Moroni since 1985; he told Musica Jazz that a 1987 Umbria Jazz performance was the turning point for the group. The album was presented at Rome's Casa del Jazz on November 30, 2023, and consists of original pieces written for jazz masters, including an opening piece for McCoy Tyner and dedications to Jim Hall and Kenny Wheeler. His latest release is Jazz Experiences (Encore Music, 2025), a duo with trumpeter Andrea Sabatino recorded in Rome on December 11 and 12, 2024. On September 19, 2021 he opened the Politeama season in Tolentino in a quintet with trumpeter Fabrizio Bosso, and a February 2026 concert at Rome's Rimessa Fab was billed as his All Stars Quartet, with pianist Roberto Tarenzi, bassist Luca Bulgarelli and drummer Lorenzo Tucci.

Alongside performing, Zeppetella teaches jazz guitar in Rome at the Percentomusica school and has given masterclasses at TolentinoJAZZ and the 52 Jazz Campus (2018). Sardinian guitarist Antonio Pitzoi lists Zeppetella among his own teachers in Percentomusica's jazz program in Rome. His official biography names Lee Konitz and Stefano Di Battista among his collaborators, though no release credit for either appears on his Discogs record.

Zeppetella's own account of his sound runs from Charlie Christian and Wes Montgomery through the bebop and hard bop of the 1960s, and a review of Handmade describes a groove-oriented player who favors single-note phrasing over chordal strumming, with lines that are clean, logical and rhythmic. His official biography adds that his range extends from straight jazz to funk and R&B. His compositional writing, from the Jobim project to the tributes on Jazz Masters, keeps a lyrical, songlike center.

In his Musica Jazz interview he describes improvisation as storytelling, valuing melodic coherence and architectural form, and says he worries that jazz increasingly prizes complexity and conceptual sophistication over emotional communication. He names Tom Harrell as an under-recognized master who shows how simplicity can move listeners deeply. His choices of collaborators follow the same taste: Kenny Wheeler's lyricism on Moving Lines, Harrell's on The Auditorium Session, and a steady run of Roman rhythm sections, Tavolazzi, Sferra, Gatto and Deidda, whose language he shares.