McLean was born in New York City. His father, John Sr., played guitar in Tiny Bradshaw’s orchestra. After his father’s death in 1939, Jackie’s musical education was continued by his godfather, his record-store-owning stepfather, and several noted teachers. He also received informal tutoring from neighbors Thelonious Monk, Bud Powell, and Charlie Parker. During high school McLean played in a band with Kenny Drew, Sonny Rollins, and Andy Kirk, Jr. (the saxophonist son of Andy Kirk).

In 1962, he recorded Let Freedom Ring for Blue Note. This album was the culmination of attempts he had made over the years to deal with harmonic problems in jazz, incorporating ideas from the free jazz developments of Ornette Coleman and the “new breed” which inspired his blending of hard bop with the “new thing”: “the search is on, Let Freedom Ring”. Let Freedom Ring began a period in which he performed with avant-garde jazz musicians rather than the veteran hard bop performers he had been playing with previously. His adaptation of modal jazz and free jazz innovations to his vision of hard bop made his recordings from 1962 on distinctive.

In 1967, his recording contract, like those of many other progressive musicians, was terminated by Blue Note’s new management. His opportunities to record promised so little pay that he abandoned recording as a way to earn a living, concentrating instead on touring. In 1968, he began teaching at The Hartt School of the University of Hartford. He later set up the university’s African American Music Department (now the Jackie McLean Institute of Jazz) and its Bachelor of Music degree in Jazz Studies program. His Steeplechase recording New York Calling, made with his son René McLean, showed that by 1980 the assimilation of all influences was complete.

In 1970, he and his wife, Dollie McLean, along with jazz bassist Paul (PB) Brown, founded the Artists Collective, Inc. of Hartford, an organization dedicated to preserving the art and culture of the African Diaspora. It provides educational programs and instruction in dance, theatre, music and visual arts. The membership of McLean’s later bands were drawn from his students in Hartford, including Steve Davis and his son René, who is a jazz saxophonist and flautist as well as a jazz educator. Also in McLean’s Hartford group was Mark Berman, the jazz pianist and broadway conductor of Smokey Joe’s Cafe and Rent. In 1979 he reached No. 53 in the UK Singles Chart with “Doctor Jackyll and Mister Funk”. This track, released on RCA as a 12″ single, was an unusual sidestep for McLean to contribute towards the funk/disco revolution of the late 1970s. Many people, at the time, in the clubs where it was played confused the female singers on the track with his name thinking he was actually female.

He received an American Jazz Masters fellowship from the National Endowment for the Arts in 2001 and numerous other national and international awards. McLean was the only American jazz musician to found a department of studies at a university and a community-based organization almost simultaneously. Each has existed for over three decades.

McLean died on March 31, 2006, in Hartford, Connecticut after a long illness. In 2006, Jackie McLean was elected to the DownBeat Hall of Fame via the International Critics Poll. He is interred in Woodlawn Cemetery, The Bronx, New York City.