John Lenwood "Jackie" McLean was born May 17, 1931, in New York City's Harlem neighborhood, the son of guitarist John McLean Sr., who played in bandleader Tiny Bradshaw's orchestra. His father died in 1939, and McLean was raised largely by his mother and a stepfather who owned a local record store, giving him early and constant access to music. He settled on alto saxophone at fifteen and studied informally with neighborhood teachers Foots Thomas, Cecil Scott, Joe Napoleon, and Andy Brown; two more of his Harlem neighbors, pianists Bud Powell and Thelonious Monk, gave him further informal tutoring. From 1948 to 1949 he played in a Harlem band alongside a teenage Sonny Rollins and pianist Kenny Drew.

McLean's stint in Miles Davis's band between 1949 and 1953 produced his first sideman recording sessions, most notably the October 5, 1951 date issued as Dig (Prestige, 1956), on which he shared the front line with Sonny Rollins over a rhythm section that included Art Blakey on drums. He made his first record as a leader on October 21, 1955, a quintet date for the small Ad Lib label released as Presenting... Jackie McLean, and spent the rest of the decade recording steadily for Prestige and its New Jazz subsidiary, including 4, 5 and 6, Lights Out!, Jackie McLean & Co., Alto Madness, and McLean's Scene, most cut at Rudy Van Gelder's Hackensack studio with regular partners Mal Waldron, Doug Watkins, and Donald Byrd. McLean later described these dates as rushed and poorly paid, even as he kept working through them; by the late 1950s, years of heroin addiction had also cost him his New York City cabaret card, the license required to perform in the city's own licensed nightclubs, which pushed him toward studio recording (a card was not required for that) rather than club work.

Through the mid-1950s McLean also built a busy career as a sideman, recording with pianist George Wallington's group and appearing on bassist Charles Mingus's 1956 Atlantic album Pithecanthropus Erectus, one of Mingus's most celebrated early leader dates. From 1956 to 1958 he was also a member of Art Blakey's Jazz Messengers, documented on albums including Hard Bop (Columbia, 1957) and A Midnight Session with the Jazz Messengers (Elektra, 1957). In 1959 and 1960 he stepped away from the bandstand to act off-Broadway in The Connection, Jack Gelber's play about heroin-addicted musicians waiting on a dealer; the production was adapted into a film in 1961.

McLean signed with Blue Note Records in 1959, beginning a contract that ran through 1967 and produced 21 albums as a leader, the core of his recorded legacy. New Soil (1959) opened the run with pianist Walter Davis Jr., bassist Paul Chambers, drummer Pete La Roca, and Donald Byrd on trumpet, and further quintet and sextet dates followed quickly: Swing, Swang, Swingin' (1960), Capuchin Swing (1960), Jackie's Bag (combining a 1959 session with pianist Sonny Clark and a 1960 session with Kenny Drew, Blue Mitchell, and Tina Brooks), Bluesnik (1961), and A Fickle Sonance (1961, again with Sonny Clark on piano). Let Freedom Ring (recorded 1962) marked a turn toward freer, more harmonically open playing, and the two albums that followed, One Step Beyond and Destination... Out! (both recorded and released 1963-64), pushed further: both dropped the piano in favor of a quintet built around trombonist Grachan Moncur III and vibraphonist Bobby Hutcherson, with drummers Tony Williams and Roy Haynes on the respective sessions. McLean kept experimenting through the rest of the decade on It's Time! (1965, with a young Herbie Hancock on piano), Right Now! (1966), Action (recorded 1964, released 1967), New and Old Gospel (1968, featuring Ornette Coleman's only recorded appearance on trumpet rather than alto sax), 'Bout Soul (1968), and Demon's Dance (recorded 1967, released 1970), which brought trumpeter Woody Shaw and drummer Jack DeJohnette into his band.

In 1967 McLean took a position as a music instructor and counselor working inside New York-area prisons, and the following year he moved to Hartford, Connecticut, to teach at the Hartt School of the University of Hartford, a post he held for the rest of his life. There he and his wife, Dollie McLean, founded the Artists Collective in 1970, a community arts and education center serving Hartford's underserved youth that moved into a purpose-built home in 1999. At Hartt, McLean established the university's African American Music Department and its jazz studies degree program, renamed the Jackie McLean Institute of Jazz on November 17, 2000; musicians who came up through the program include saxophonist Antoine Roney, drummer Eric McPherson, trombonist Steve Davis, and pianist Alan Palmer, and his own son, saxophonist and flutist Rene McLean, became a regular member of his later working bands. Recording slowed but never stopped: a run of SteepleChase albums made in Copenhagen in the 1970s (Live at Montmartre, Antiquity, and others), a brief detour onto RCA (Doctor Jackyll and Mister Funk and the orchestral Monuments, both 1979), and a return to more active performing in the 1980s and 1990s produced Dynasty (1988, Triloka), Rhythm of the Earth (1992, Antilles/Birdology, with trumpeter Roy Hargrove), and Hat Trick (1996) and Nature Boy (1999), the latter two made for Blue Note's Japanese Somethin' Else imprint and closing his studio discography alongside pianist Cedar Walton and drummer Billy Higgins.

McLean received an American Jazz Masters fellowship from the National Endowment for the Arts in 2001 and was elected to DownBeat's Hall of Fame via its 2006 Critics Poll. He passed away at his home in Hartford on March 31, 2006, after a long illness, at age 74, and is buried at Woodlawn Cemetery in the Bronx.

McLean forged one of the most instantly identifiable voices in jazz saxophone: a hard, slightly sharp-edged tone that colleagues and critics could pick out within two notes, paired with an urgent, vocal-like phrasing rooted equally in Charlie Parker's bebop vocabulary and in the blues. He was among the relatively few bebop-formed altoists of the 1950s to absorb the freer language of 1960s avant-garde jazz without abandoning hard bop's underlying structure, a synthesis heard most clearly on One Step Beyond and Destination... Out!. Those mid-1960s Blue Note albums, and the pianoless small-group format he built around Grachan Moncur III and Bobby Hutcherson, are widely credited with opening a path between Ornette Coleman's freedoms and mainstream hard bop, an influence he extended directly for decades afterward through the jazz program he founded at the Hartt School, which trained musicians including Antoine Roney, Eric McPherson, and Steve Davis.