Antonello Salis was born on February 28, 1950 in Villamar, an inland village of roughly 2,900 people in the province of Cagliari, in central Sardinia. His grandfather gave him a toy accordion when he was seven, and he learned it without a teacher. He taught himself the piano the same way, and later the Hammond organ. He left school early to work and help support his grandparents, and he has never held a conservatory qualification of any kind.

His working life started in the Sardinian dance-hall and beat-group circuit. In 1967, while waiting tables in Portoscuso, he joined a band called Black Strings, then Los Sardos, then Nati Stanchi. In 1969 he joined I Barrittas under Benito Urgu, a run that ended after military service took him out of circulation from February 1970.

The group that gave him a direction was I Cadmo, formed in Alghero in 1973 with Riccardo Lay on bass and Mario Paliano on drums. The trio sat between progressive rock and free jazz and moved to Rome in 1975, the year Salis played his first solo piano concert at the city's jazz festival at Castel Sant'Angelo. Boomerang appeared on Vedette Records with liner notes by the critic Franco Fayenz, followed by Flying Over Ortobene Mount in July Seventy-Seven, which added the alto saxophonist Massimo Urbani. The band later expanded into the quintet G.R.A. with Sandro Satta and Danilo Terenzi, and wound up in 1982.

Rome gave him the American connection that shaped his playing. From 1978 he shared stages at the Cinema Adriano with Lester Bowie, Famoudou Don Moye and Roscoe Mitchell of the Art Ensemble of Chicago, and from 1979 he played in the bassist Marcello Melis's quartet at the Music Inn, the club where he encountered Charles Mingus and Ornette Coleman. His first co-billed record, Old Fashioned, was made with the Roman free-jazz altoist Mario Schiano at Studio Junior in Rome on June 5, 1978.

In 1980 the Swiss label Hat Hut released Orange Juice / Nice Food, recorded live at the University of Zurich on February 4 of that year. Two long tracks of solo piano, catalogued as free improvisation, it is the first record to carry his name alone.

What followed was a career built out of duos. Salis has made two-person records with the Brazilian percussionist Naná Vasconcelos (Lester, Soul Note, cut at Milan's Barigozzi Studio on December 9 and 10, 1985), the French guitarist Gérard Pansanel (Cinecittà, 1987, and Beatles Stories, 1991), the alto saxophonist Sandro Satta (Live in Como, taped at the Jazz & Co. festival on July 17, 1993, and Live @ Radiotre, 2001), the pianist Riccardo Fassi (Joining, 1986, and Totem, recorded at Vatican Radio on April 19, 1995), the British free-improvisation saxophonist Evan Parker (Improvvisazioni, 1995, and True Live Walnuts, 1998), the trombonist Gianluca Petrella (Rinoceronti sul Limbara, 2003), the guitarist Paolo Angeli (MA.RI, Auand, 2004), the American drummer Joey Baron (Keys and Skins, CAM Jazz, 2008) and the trumpeter Fabrizio Bosso (Stunt, Parco della Musica, 2008). He also holds a place in the accordion lineage proper, recording Vignola Reunion Trio in 1996 alongside Marcel Azzola and Richard Galliano.

The Sardinian strand of his work runs in parallel and never reduces to local colour. Sonos 'e Memoria, recorded live on April 29 and 30, 1996 and released by ACT in 2001, was written as the soundtrack to Gianfranco Cabiddu's film of the same name. It places Salis's accordion alongside Luigi Lai on launeddas, the singer Elena Ledda, Mauro Palmas on mandola and the confraternity choir Su Concordu 'e su Rosariu of Santu Lussurgiu, under Paolo Fresu's musical direction with Furio Di Castri on bass. Fourteen years later, Giornale di Bordo, cut in Cagliari between February 15 and 17, 2010, set him beside Paolo Angeli's self-built prepared Sardinian guitar, Gavino Murgia singing the bassu line of Sardinian polyphony, and Hamid Drake on frame drum.

Pianosolo, recorded at Artesuono Studio in Cavalicco on December 1 and 2, 2005 and released by CAM Jazz in 2006, is his defining solo statement. Its instrument credit reads "concert grand piano, piano (prepared), whistling, noises (gurgles and grunts)", and the programme mixes his own compositions with Nino Rota and with pieces by Riccardo Lay, his old bassist from I Cadmo. Paolo Fresu wrote the liner notes.

The recognition arrived in the middle of the 2000s. Salis took the Django d'Or in 2005 and a career award from the European Jazz Expo in 2008. Musica Jazz's Top Jazz poll named him best keyboard instrumentalist of 2008 and voted Stunt, his duo with Fabrizio Bosso, album of the year.

In recent years he has kept working at both scales. Jazz (R)evolution (2015) reunited him with Famoudou Don Moye alongside the Malian griot Baba Sissoko, taped live in Bari on November 28, 2014. In May 2025, Parco della Musica Records released Cum Grano Salis, recorded at Rome's Casa del Jazz across June 27 to 30, 2023, on which Riccardo Fassi orchestrated Salis's own compositions for his seventeen-piece Tankio Band and wrote him "Random Sequencer", a piano concerto with a solo cadenza, thirty-nine years after their first record together. Three months earlier, on February 17, 2025, Salis had played the Teatro Politeama Rossetti in Trieste in an ensemble Stefano Bollani assembled with Enrico Rava, Paolo Fresu, Roberto Gatto, Ares Tavolazzi, Daniele Sepe, Matteo Mancuso, Christian Mascetta and Frida Bollani Magoni. That concert was released as Tutta Vita Live on March 20, 2026 and closes Valentina Cenni's documentary Tutta Vita.

His Discogs entry carries 202 credits, of which 44 are leader or co-leader releases and 125 are appearances on other people's records.

Salis is a physical improviser before he is a stylist. He plays the piano from inside as readily as from the keyboard, plucking and striking the strings directly, and the prepared piano is a standing part of his instrument rather than an occasional effect: Salis! (1987) lists "prepared Steinway" as a credit separate from "Steinway", and Keys and Skins (2008) credits piano and prepared piano side by side. Mid-piece he will leave the keyboard for the accordion, which he treats as a percussion instrument and a set of bellows at least as often as a melodic one.

His formation was oral rather than academic, and it shows in the repertoire he keeps returning to. He works from song material (the Beatles, Nino Rota, Thelonious Monk, John Coltrane, Joe Zawinul, Jimi Hendrix, the Italian popular songbook) and dismantles it live rather than arranging it in advance. The Art Ensemble of Chicago musicians he met in Rome in the late 1970s, particularly Lester Bowie and Famoudou Don Moye, are the clearest external influence on that approach, and Evan Parker is the improviser he has recorded with most often outside Italy.

The other half of his language is Sardinian. Launeddas polyphony, cantu a tenore singing and the island's dance rhythms sit inside his playing as working material rather than quotation, which is why records like Sonos 'e Memoria and Giornale di Bordo put folk musicians and jazz musicians on the same stand instead of layering one over the other.