Bennie Maupin was born on August 29, 1940, in Detroit, Michigan. He played piano by ear as a small child, took up clarinet, and moved to saxophone in his teens. He studied at the Detroit Institute of Musical Art, finishing in the spring of 1962, and took flute lessons with Larry Teal. He has named Yusef Lateef, who also came up in Detroit, as a model for working across several reeds and flutes, and he heard John Coltrane and Eric Dolphy when they came through the city; Dolphy gave him a flute lesson that he remembered as a formative moment.

In 1962 he went to New York with the Four Tops, left the group, and stayed. He took a hospital job that he held for about three years while he found his place on the scene, and it was in New York that he took up bass clarinet, the instrument most associated with him. His first notable recordings were with the alto saxophonist Marion Brown, on the Marion Brown Quartet (ESP-Disk, 1966) and Juba-Lee (Fontana, 1967). He also worked with Roy Haynes in the mid-1960s, joined Freddie Hubbard's band in 1967, recorded with McCoy Tyner on Tender Moments (Blue Note, 1968), and played with Horace Silver in 1968 and 1969 on Serenade to a Soul Sister and You Gotta Take a Little Love. From 1968 he was a regular in Lee Morgan's group, appearing on Caramba! (1968) and Live at the Lighthouse, recorded in 1970.

Through the drummer Jack DeJohnette he was brought into the Bitches Brew sessions led by Miles Davis in August 1969, where he played bass clarinet on five tracks of the double album. He returned for On the Corner (1972), played on further Davis sessions later collected in The Complete Jack Johnson Sessions (2003), and is also heard on Big Fun (1974). In 1970, when Davis asked him to join his touring band, he declined because he had already committed to Morgan.

That same year Herbie Hancock formed a sextet that took the name Mwandishi, with Maupin, trumpeter Eddie Henderson, trombonist Julian Priester, bassist Buster Williams and drummer Billy Hart. The band recorded Mwandishi (1971), Crossings (1972), which included two Maupin compositions, and Sextant (1973). When Hancock dissolved it and built a funk band, Maupin was the only member of the sextet he kept, and he is heard on Head Hunters (1973), where he plays the lead melody of "Chameleon" and bass clarinet on the closing "Vein Melter." He stayed with Hancock through Thrust (1974) and later records including Man-Child (1975), Secrets (1976), Sunlight (1978) and Mr. Hands (1980), and rejoined him for Dis Is da Drum (1994). He also appears on albums by the Headhunters themselves, from Survival of the Fittest (1975) to Return of the Headhunters (1998). In 1970 he became a practitioner of Buddhism.

His first record as a leader, The Jewel in the Lotus (ECM, 1974), was recorded in March 1974 at the Record Plant in New York with Hancock, Williams, Hart, Freddie Waits and Bill Summers. He settled in California in the 1970s. In 1977 and 1978 he made two albums for Mercury, Slow Traffic to the Right and Moonscapes, both produced by Patrick Gleeson. A session he had recorded in 1967 with the pianist Mike Nock, Cecil McBee and drummer Eddie Marshall, billed as Almanac, was issued in 1977. He studied composition and orchestration with Lyle "Spud" Murphy around 1978, and his output as a leader slowed in the 1980s and 1990s. Driving While Black (Intuition, 1998), a duo project with Gleeson, marked his return, followed by Penumbra (Cryptogramophone, 2006), a quartet date with bassist Darek Oleszkiewicz and drummer Michael Stephans, and Early Reflections (Cryptogramophone, 2008), recorded in Warsaw with a Polish quartet. In 2022 he and the percussionist Adam Rudolph released Symphonic Tone Poem for Brother Yusef (Strut), a tribute to Lateef. He has also taught at the California Institute of the Arts.

In January 2025 the Eaton Fire destroyed his home in Altadena, California, where he had lived for about 30 years, along with his instruments and his music. He escaped unhurt, and a fundraising campaign was set up to help him and his family recover.

Maupin is better known as a colorist and an ensemble player than as a showcase soloist: his bass clarinet and alto flute set the atmosphere on Bitches Brew and Head Hunters, and on The Jewel in the Lotus he writes for a rhythm section of piano, bass and three percussionists so that the players converse rather than trade solos. Critics have called that album a classic of 1970s spiritual jazz and compared its sound-world with Bitches Brew and early Weather Report, and AllMusic gave it five stars. His improvising has been described as harmonically advanced and "out," yet with a different sense of melodic direction from that of Eric Dolphy, whom he heard in Detroit and cites as a formative influence along with Yusef Lateef and John Coltrane. His later records include a piece for Dolphy on Penumbra and the five-movement Symphonic Tone Poem for Brother Yusef, which uses reeds, flutes, keyboards and percussion in a long-form duo with Adam Rudolph.