Leonard Joseph Tristano was born in Chicago on March 19, 1919, the second of four brothers; his father, Michael, had come from Italy as a child. He began on the family's player piano at two or three and took classical lessons from the age of eight, which he later said held him back more than they helped. His eyesight was poor from birth, and by nine or ten he was totally blind from glaucoma. From about 1928 he spent a decade at the Illinois School for the Blind in Jacksonville, where he played saxophones, trumpet, guitar and drums as well as piano, and he had his first gigs at eleven, on clarinet. He studied performance at the American Conservatory of Music in Chicago from 1938 to 1941 and stayed two more years of graduate study, leaving before he finished a master's degree.

In the early 1940s he played tenor saxophone and piano in a range of Chicago jobs, including a rumba band, and began giving lessons, among his first pupils the alto saxophonist Lee Konitz. From 1943 he also taught at the Axel Christensen School of Popular Music. He won press notice in Metronome in 1944 and in Down Beat from 1945, and that year he recorded solo piano and made records with musicians from Woody Herman's band. In 1946 he moved to New York, first stopping on Long Island at Freeport, where he played a restaurant job with guitarist Billy Bauer and bassist Arnold Fishkin. That trio recorded in 1946 and 1947, including Keynote sides cut on October 8, 1946, and May 23, 1947; reviewers noted the counterpoint between piano and guitar, and Gunther Schuller later called one of the pieces too far ahead of its time. Tristano met Charlie Parker in 1947 and played with him on WOR radio broadcasts in September and November of that year, in bands that included Dizzy Gillespie and Max Roach. He was named Metronome's musician of the year for 1947.

By 1948 he had added Konitz and a drummer to make a quintet, and the tenor saxophonist Warne Marsh, another pupil, soon joined. In 1949 the group made two sets of recordings that proved decisive. At sessions for Capitol on March 4, March 14 and May 16, the sextet recorded original lines such as "Wow" and "Crosscurrent" on familiar chord changes, and on May 16 the five musicians, without a drummer, recorded "Intuition" and "Digression". Only the order of entrances and their rough timing was agreed beforehand; harmony, key, tempo and melody were left open, and the players were held together by contrapuntal interaction. They are generally cited as the first group free improvisations on record. "Intuition" came out late in 1950 and "Digression" not until 1954. Parker and the composer Aaron Copland admired them, while many musicians of the day found the music too cold. The sextet played the opening night of Birdland and a five-week stay there, but work was scarce.

In 1951 Tristano moved his teaching from his home in Flushing, Queens, to a Manhattan loft at 317 East 32nd Street, part of which he turned into a recording studio, and he started a small label, Jazz Records, which issued a single 45 in 1952, pairing "Ju-Ju" and "Pastime" by a trio with bassist Peter Ind and drummer Roy Haynes, recorded on October 30, 1951, with second piano parts that Tristano overdubbed afterward; Ind described them as the first improvised overdubbed jazz recordings. A quintet with Konitz, Marsh, Ind and drummer Al Levitt was recorded live in Toronto on July 17, 1952. Konitz joined Stan Kenton that summer, which broke up the core of the group. In 1953 Tristano made "Descent into the Maelstrom," a solo piano piece drawn from Edgar Allan Poe's story, improvised by developing motifs with multitracking rather than working over a chord sequence. His sextet played the first Newport Jazz Festival in 1954, probably his only festival, since he thought them too commercial. He made his first Atlantic album, Lennie Tristano, in 1954 and 1955, with control over what was made and issued. Its first four tracks, including "Line Up," "Requiem," a tribute to Parker, and "East Thirty-Second," used overdubbing and altered tape speed, which drew criticism when it appeared in 1956; the rest was recorded live at the Confucius Restaurant in Manhattan on June 11, 1955, with Konitz, bassist Gene Ramey and drummer Art Taylor.

From the mid-1950s Tristano put teaching ahead of performing. He lost his Manhattan studio in 1956 and set up a new one in Hollis, Queens. From 1958 he played engagements at New York's Half Note, where the owners persuaded him to appear in part by replacing the house piano with a Bechstein of his choosing; a live recording from 1958 has Marsh, bassist Henry Grimes and drummer Paul Motian. His second Atlantic album, The New Tristano (recorded 1961, issued in 1962), was all unaccompanied piano with no overdubbing or tape speed. In 1964 he reunited the quintet with Konitz and Marsh for two months at the Half Note and played Toronto's Coq d'Or. He toured Europe as a mostly solo pianist in 1965, a trip that included a Berlin concert of six pianists on October 30 with Earl Hines, Teddy Wilson, John Lewis, Bill Evans and Jaki Byard, and a solo concert at Copenhagen's Tivoli Gardens on October 31. He returned to England in 1968 with Ind and again in 1969; his last public performance in the United States was in 1968. In the 1970s he turned down concert offers and kept teaching, to a total of pupils that may exceed a thousand over three decades, while eye pain and emphysema wore him down. He passed away of a heart attack at his home in Jamaica, New York, on November 18, 1978, at the age of 59. He was elected to the Down Beat Hall of Fame in 1979, and Crosscurrents entered the Grammy Hall of Fame in 2013.

Among saxophonists his early models were Lester Young and Charlie Parker, and among pianists Art Tatum; he also admired Bud Powell's articulation. His own playing favored long, nearly even eighth-note lines with small rhythmic displacements rather than bebop's sharp accents, strict time against which he layered changes of meter, block-chord passages, and in the 1950s a form of side-slipping, temporary bitonality made by laying chromatic harmony over standard changes. Grove's entry singled out his mastery of several levels of double time, and pianist Ethan Iverson has ranked him in the top tier for technique. His left hand often carried a walking bass line while the right hand improvised against it, as on The New Tristano. The cool-jazz label is only a partial description: the group improvisations of 1949 were an early step toward free playing, and the atonal, motif-driven "Descent into the Maelstrom" of 1953 anticipated later work by pianists such as Cecil Taylor and Borah Bergman.

As a teacher he is one of the first to have taught jazz improvisation in a structured way, in short individual lessons of fifteen to twenty minutes in which pupils sang and then played the solos of Young and Parker, worked with a metronome set very slow and gradually sped up, and learned tunes in all keys; he taught the same method to players of any instrument. His best-known pupils were Lee Konitz and Warne Marsh, and the painter Robert Ryman also took lessons; the singer Sheila Jordan, the saxophonist Phil Woods and the saxophonist Dave Liebman each studied with him, according to their own profiles. Elements of his early work, counterpoint, reharmonization and strict time, are heard in Miles Davis's Birth of the Cool and in the playing of Gerry Mulligan and Dave Brubeck; Bill Evans later used overdubbing after Tristano's experiments, and Anthony Braxton has often named him and his students as influences. Mose Allison said Tristano and Powell were the founders of modern piano playing, and the writer Thomas Albright counted him among the influences on Paul Bley, Andrew Hill, Mal Waldron and Taylor. Critics are divided: some heard his playing as cold and his innovations as having little impact, others call him a bridge from bebop to freer forms who has been underrated because he refused to commercialize and was hard to categorize.