Born and raised in Naples in the Piscinola - Marianella district, he studied saxophone and began performing in public at the age of seven. He later graduated in flute from the San Pietro a Majella Conservatory. In the years 1976-1977 he collaborated with Pino Daniele on the album Terra mia; his collaboration with Edoardo Bennato dates back to 1979-1980, for the 1980 albums Uffà! Uffa! and sono solo canzoni. In 1982 he released his first record as a leader entitled Avitabile, consisting of nine tracks, including a dedication to his late friend Mario Musella, Dolce dolce "M". In 1983 he released Better soul with tracks such as Charlie, in reference to Charlie Parker, Gospel mio, sung with Richie Havens and When I guess. The following year Corre was released, dedicated to his daughter Connie, again for the record label EMI Music. 1986 saw the release of SOS brothers, which contains the song Mamma Che Caos (also released in a remix version), Soul express and Black Out, which in the remix version would win an award in Ibiza as best dance song of the year. The cover of the record was created in comic book style by Andrea Pazienza. His meeting with James Brown was enlightening when Avitabile was chosen to open his concerts in Italy. It was Brown who told Avitabile: .. "start again from your land", and so Avitabile changed his vision of music. In 1988 he released High Voltage, the title of the album's homonymous song and a collaboration with Afrika Bambaataa for the album Street Happiness. In 1990, however, Stella dissidente with a cover by Milo Manara. The following year Enzo Avitabile released an album with the same title, with the collaboration of Corrado Rustici. In 1994 Easy was released where he set to music "'A livella" by Totò and sang in a duet with Randy Crawford Leave me or love me. In 1995 he wrote the music for E c'è ancora la canzone del mare sung by Giorgia contained in the singer-songwriter's album Come Thelma & Louise. The attention paid to rap and jungle music and the return to the use of Neapolitan in the lyrics led to the creation of Addò in 1996. O-issa, a 1999 album, contains the single "Mane e Mane", written with Mory Kante; a portion of the proceeds will go to support the UNICEF initiative to guarantee the right to schooling for girls in Benin. Twelve tracks and two remixes, the two songs written with the African artist, Mane e Mane (Kelendi-Kelendi) and O-issa. In 2000 he began his collaboration with producer and manager Andrea Aragosa and his first experiments with the Bottari di Portico. Since 2003 he has been artistic director of the International World Music Festival "Sentieri Mediterranei" and since 2015 of the Leuciana Festival. In 2004 Salvamm''o munno was released, a record in which Khaled, Manu Dibango, I Bottari di Portici, Amina, Simon Shaeen, Hugh Masekela, Luigi Lai, Cantori del Miserere di Sessa Aurunca and Baba Sissoko collaborate, the liner notes of his acts are signed by the anthropologist Marino Niola. In 2005 and 2006 he received 4 nominations at the BBC World Music Awards. In 2006 an introspective recording project was released, Sacro Sud, a journey in which the author, through sacred and spiritual music starting from Saint Alphonsus Maria De Liguori, is led to explore the suburbs of the soul. In 2007 the double cd Festa, farina e forca was released with the collaboration of Manu Dibango in the reinterpretation of Soul Makossa, the second disc entirely dedicated to remixes saw the participation of Matthew Herbert, Ludovic Llorca, Bill Laswell, Gigi, Fredric Galliano, Banco De Gaia, Polo, Tempio del Suono. In 2009 a second special Neapolitan project was released with which he won the Targa Tenco for the best dialect album. In 2012 the album Black Tarantella was released, which saw the participation of Pino Daniele, Francesco Guccini, Franco Battiato, David Crosby, Bob Geldof, Enrique Morente, Idir, Toumani Diabate', Mauro Pagani, Co'Sang, Raiz. He won his second Targa Tenco 2012 for the best dialect album and the Premio Lunezia 2012 for the musical-literary value of the album "Black Tarantella". Also in 2012, director Jonathan Demme dedicated a docufilm to him which was presented at the Venice Film Festival, Enzo Avitabile Music Life. In 2012 the soundtrack of Enzo Avitabile Music Life was released, with the participation of many artists. In 2013 he was present on the first solo album (Il Courage Impossible) of his nephew and rapper Ntò, on the track Se ti avessi ora. In 2016 Lotto infinito was released for Sony Music, which saw meetings with Francesco De Gregori, Renato Zero, Giorgia and many others. He has written over 300 works for quartets, chamber and symphony orchestras, and is the author of the music for symphony orchestra and choir of Pippo Del Bono's opera Il Vangelo. Throughout his career he has performed at various events such as Womad Festival, London Jazz Festival, Umbria Jazz, Montreal Jazz Festival, Sziget Festival, Primo Maggio, New Year's Concert in Naples, with tours all over the world. On March 27, 2017 he won two David di Donatello awards for the soundtrack of the film Indivisibili by Edoardo De Angelis: Best Musician and Best Original Song (Abbi pietà di noi). On July 1, 2017 he also won at the Nastri d'Argento. A year later he was called to participate in the Sanremo Festival 2018 paired with Peppe Servillo in the Champions category with the song Il coraggio di ogni giorno, finishing twelfth. In 2019 he won the Nastro d'argento for the best soundtrack, included in the film Il vizio della speranza. Also this year his collaborations with Kamasi Washington and Marcus Miller and a tour of 100 concerts, including the one held at the Ravenna Festival with Francesco De Gregori and Tony Esposito. He also curated the artistic direction of the SETTEMBRE AL BORGO festival, now in its 46th edition, and that of SACRO SUD -ANIME SALVE, in its 2nd edition. In 2022 he was a guest on Jovanotti's track "Corpo a corpo", included in his album 'Mediterraneo'.