Born in Harlem, McLean was the son of a jazz guitarist and grew up surrounded by jazz musicians; modern-jazz legends Thelonious Monk, Bud Powell, and Charlie Parker, who lived nearby, were mentors. While still a teenager, he performed and recorded with Sonny Rollins and Miles Davis; he later appeared with Charles Mingus and Art Blakey. In 1955, he recorded his first album as a leader, with Donald Bryd, Mel Waldron, and others.
Initially, McLean's style was similar to Parker's; in the 1960s, he embraced the "free jazz" of Ornette Coleman.
In 1970, McLean began teaching at the Hartt School of music at the University of Hartford. He eventually founded the African-American Music program there, one of the first degree programs dedicated to jazz, according to the Times. It is now known as the Jackie McLean Institute of Jazz.
He received the NEA Jazz Master award, the nation's highest honor for jazz musicians, in 2001.