Gaetano "James" Senese was born in Naples on January 6, 1945, to Anna Senese and James Smith, an American soldier from North Carolina who was stationed in Italy during the war and went back to the United States about eighteen months after his son's birth. Senese grew up in the Miano district with his maternal grandfather and heard jazz and swing on records that American servicemen brought to the city. A John Coltrane record pointed him toward the saxophone, and his mother gave him one when he was twelve. He learned the basics under a local teacher, Pasquale Santoro, and played in the town band of Piscinola.

His professional start was in Neapolitan rhythm and blues. After a 1961 group in Terzigno with singer Mario Musella and a 1963 outfit, Vito Russo e i 4 Conny, that cut singles for King, he joined drummer Franco Del Prete in 1965 to found The Showmen. The band covered Otis Redding, James Brown and Marvin Gaye, won the 1968 Cantagiro with "Un'ora sola ti vorrei," and made an LP for RCA Italiana in 1969 on which Senese is credited with vocals, tenor and baritone saxophones, flute and percussion. When the group broke up, Del Prete and Senese kept going as Showmen 2 and recorded an album in 1972.

In 1974 the pair started something more ambitious, the jazz-rock band Napoli Centrale. The group sang in Neapolitan dialect over a fusion rhythm section, with the American keyboardist Mark Harris and the English bassist Tony Walmsley in the first lineup. Napoli Centrale (Dischi Ricordi, 1975), recorded in Rome, carried the single "Campagna" and, by Rolling Stone Italia's account, sold about 90,000 copies. Harris and Walmsley left soon afterward to join Il Rovescio della Medaglia, and a rotating cast followed. Italian reference sources place the band in concerts in Rome with Weather Report and with the band co-led by Billy Cobham and George Duke, and at the Montreux Jazz Festival. Mattanza (1976) added the drummer Agostino Marangolo and the bassist Kelvin Bullen, and a young Pino Daniele passed through the band as bassist. After Napoli Centrale's first run ended, Senese began the long collaboration with Daniele for which most Italians know him, as the tenor saxophonist on Pino Daniele (1979), Nero a metà (1980) and Vai mò (1981).

The solo career began with James Senese (Polydor, 1983) and Il passo del gigante (Tobacco, 1984), both issued while Napoli Centrale sat idle. Alhambra (1988), produced by Willy David, was the most ambitious of them: Gil Evans is credited with orchestrations and electric piano, the album opens with "Love Supreme," a homage to Coltrane, and the instrumental "Alhambra (Memento per Gil Evans)" honors the arranger. In 1990 Senese played the Apollo Theater in New York, where he was introduced as a "brother in soul." Hey James (Blue Angel, 1991) was dedicated to the father he never knew, and in 1992 he revived Napoli Centrale for Jesceallàh, on which Lester Bowie and Famoudou Don Moye of the Art Ensemble of Chicago are credited on two tracks. The band's records continued with 'Ngazzate nire (1994) and Zitte! Sta arrivanne 'o mammone (2001), and the solo albums with Sabato Santo (2000), Passpartuù (2003) and Tribuù e passione (2003), the last one shared with the Neapolitan singer-songwriter Enzo Gragnaniello.

Senese went on recording into his seventies. 'O sanghe (2016) won the Targa Tenco for best album in dialect, and Aspettanno 'o tiempo (2018) documented the band live. A documentary, James, directed by Andrea Della Monica, premiered at the 77th Venice International Film Festival in 2020, and James Is Back followed in 2021. Stiamo cercando il mondo came in 2023, and his last album, Chest nun è 'a terra mia, was released on Arealive in May 2025. He was admitted to Naples's Cardarelli Hospital on September 24, 2025, and passed away there of pneumonia on October 29, 2025, at the age of 80. The funeral was held at the Madonna dell'Arco church in Miano.

Senese's sound starts from a Coltrane-rooted tenor and soprano saxophone, often paired in his later records with a wind synthesizer, set against funk and soul grooves and sung in Neapolitan. Napoli Centrale put that voice inside a jazz-rock rhythm section at a time when most Italian bands working in that territory sang in standard Italian, and Rolling Stone Italia calls its debut a key influence on the Neapolitan music that followed, the blend of blues, funk and local song that Pino Daniele later took to a mass audience. This is jazz-adjacent music in the plainest sense. His records sit between jazz fusion, soul-jazz and Neapolitan song, and his reputation in Italy rests as much on the song side as on the jazz credits. The jazz side is nonetheless documented and substantial: a fusion band that played Rome stages with Weather Report, an album that features Gil Evans and opens with a homage to John Coltrane, trumpet and percussion from the Art Ensemble of Chicago, and decades of records that Discogs files under jazz-rock, jazz-funk and soul-jazz.