Simone Zanchini was born in 1973 in Novafeltria, in the Emilia-Romagna/Marche border region, and now lives in nearby San Leo. He started on folk accordion at age eight, influenced by an uncle, and spent years through age twenty-two playing in Romagna's traditional "liscio" dance halls before turning to the classical repertoire. He earned an honors diploma in classical accordion from the Conservatorio "G. Rossini" in Pesaro under Sergio Scappini in 1998, among the first graduates of a classical accordion program the conservatory had only started in 1992. Since 1999 he has been the first accordion for the Ensemble Strumentale Scaligero, the soloists' ensemble of Milan's Teatro alla Scala, performing contemporary concert repertoire including works by Richard Galliano.

Zanchini has described himself as one of the musicians who pushed the accordion into bebop-derived jazz improvisation and live electronics, territory the instrument held marginal status in decades ago. He made his first recorded appearance in 1997 with the self-released Quartetto Magritte album Le Vacanze Di Hegel, and has released roughly twenty albums since, split between jazz, contemporary/electroacoustic improvisation, classical crossover, tango and Sardinian sacred vocal music.

His most sustained jazz partnership is with clarinetist Gabriele Mirabassi: the two first recorded together in the trio Basso Profilo with bassist Giovanni Tommaso (2011, C.A.M. Jazz), then as a duo on Il Gatto E La Volpe (2021, EGEA) and Un Ballo Con La Luna (2023, EGEA). Zanchini also leads the Simone Zanchini Jazz Quartet, with saxophonist Stefano Bedetti, bassist Stefano Senni and drummer Zeno De Rossi, heard on Casadei Secondo Me (recorded live at the 2013 Ravenna Festival, released 2015 on Stradivarius), a set of jazz arrangements of Romagna dance-band composer Secondo Casadei. A separate trio with clarinetist/saxophonist Daniele D'Agaro and trombonist Mauro Ottolini produced Up & Down (2012, Artesuono).

With Croatian guitarist Ratko Zjaca, bassist Martin Gjakonovski and American drummer Adam Nussbaum, Zanchini recorded The Way We Talk (2010), Beyond The Lines (2013, as ZZ Quartet) and Midnight In Europe (2021, as ZZ Quartet), all on the German label In+Out Records. His own leader date Don't Try This Anywhere (2015, In+Out Records) is a tribute to saxophonist Michael Brecker, recorded in New York with Nussbaum (Brecker's original drummer on 1988's Don't Try This At Home), bassist John Patitucci and saxophonist Stefano Bedetti; it won the Orpheus Award for best album in Italy in 2016. He recorded a full-length duo album with American jazz accordionist Frank Marocco, Be-bop Buffet (2006, Wide Sound), and separately paid tribute to Marocco and Art Van Damme on the quintet session Fuga Per Art (2008, Dodicilune), with vibraphonist Andrea Dulbecco, guitarist Giancarlo Bianchetti, bassist Stefano Senni and drummer Massimo Manzi.

Away from the jazz quartet format, Zanchini has pursued solo electroacoustic improvisation on Better Alone...! (2008) and My Accordion Concept (2012), both for Silta Records, built on live electronics paired with acoustic accordion. He has also worked extensively in classical-adjacent and world-music settings: the tango repertoire of Astor Piazzolla with the Modern Saxophone Quartet (Imagenes De Tango, 2000, Velut Luna) and with saxophonist Mario Marzi and pianist Paolo Zannini (Tango Y Algo Mas, 2003); a setting of Sardinian liturgical polyphony with saxophonist Enzo Favata and the vocal ensemble Cuncordu di Castelsardo (Boghes And Voices - The Sacred Mystery Of Sardinia, 2002, Symphonia); and, in 2019, a big-band commission arranging Nino Rota's film scores for the Frankfurt Radio Big Band under conductor David Grottschreiber (Play The Music Of Nino Rota, In+Out Records). His trio GONE, with Gianluca Lusi and Luigi Masciari, released an album of the same name in 2022 on Tosky Records.

As a side musician Zanchini has also recorded with pianist Dimitri Sillato on Voci. Tre Grandi Poeti In Musica (2010), a song cycle setting Romagna dialect poets Tonino Guerra, Raffaello Baldini and Nino Pedretti; with the Romagna wind ensemble Banda Olifante (2009, Felmay); with Croatian vocalist Tamara Obrovac's Transhistria Ensemble on Sve Pasiva - All Fades Away (2003); with Macedonian saxophonist Vasko Atanasovski's Adrabesa Quartet on Phoenix (2020, MoonJune Records); and on the soundtrack to Ferzan Ozpetek's film Saturno Contro (2007), composed by Neffa.

Zanchini's own catalog sits across two connected but distinct strands. The jazz strand runs from bebop and swing repertoire (Be-bop Buffet, the Michael Brecker tribute Don't Try This Anywhere) through contemporary small-group writing with his quartet and with Mirabassi, Discogs tagging most of these releases plainly "Jazz" and several "Contemporary Jazz." A second, free-improvisation-leaning strand runs through his solo electroacoustic records Better Alone...! and My Accordion Concept, built on live electronics layered over acoustic accordion, and continues into the trio GONE, whose 2022 album carries Discogs style tags of "Free Improvisation" alongside "Contemporary Jazz" and "Swing."

A third, classical-crossover identity runs alongside both: since 1999 he has held the first-accordion chair with the Ensemble Strumentale Scaligero at Teatro alla Scala, and his tango records with the Modern Saxophone Quartet and with Mario Marzi and Paolo Zannini are genre-tagged "Latin"/"Tango" and "Classical" on Discogs rather than jazz. Boghes And Voices, his Sardinian sacred-music project with Enzo Favata, is tagged a mix of "Jazz," "Classical" and "Folk, World & Country," which captures how closely those idioms sit together across his catalog as a whole. That same classical-jazz overlap shows up in his 2019 Frankfurt Radio Big Band commission, where he arranged Nino Rota's film scores, music written for the concert hall and the screen, into a jazz big-band format.