William Thomas Strayhorn was born on November 29, 1915, in Dayton, Ohio, and grew up in the Homewood neighborhood of Pittsburgh, Pennsylvania. His mother sent him for long stretches to her family's home in Hillsborough, North Carolina, to keep him away from his father's drunken rages, and it was at his grandmother's house there that he first played hymns on her piano and listened to records on her Victrola. Back in Pittsburgh as a schoolboy, he took odd jobs to pay for his first piano and studied with Charlotte Enty Catlin. At Westinghouse High School, which also produced Erroll Garner and Ahmad Jamal, he played in the school band and studied with Carl McVicker, a teacher of Garner and Mary Lou Williams as well. He took classical studies at the Pittsburgh Music Institute, wrote a musical, led a trio that played daily on a local radio station, and wrote "Life Is Lonely" (later renamed "Lush Life"), "My Little Brown Book" and "Something to Live For." By nineteen he was writing for a professional show, Fantastic Rhythm.

He had hoped to become a classical composer, but the concert world of the 1930s offered little room for a Black musician. Hearing Art Tatum and Teddy Wilson at nineteen pushed him toward jazz, and he played around Pittsburgh in a combo called the Mad Hatters and, from 1937, wrote arrangements for Buddy Malone's dance band. He had seen Duke Ellington play in Pittsburgh in 1933 and met him in December 1938, when the band returned. Strayhorn explained how he would have arranged one of Ellington's own pieces, then showed him, and Ellington was impressed enough to bring members of the band in to listen. In early 1939 he moved to New York to work for Ellington, reportedly with no contract or formal agreement, as an arranger, composer, occasional pianist and collaborator. Through Ellington's son Mercer he met the musician Aaron Bridgers, his first partner, with whom he lived until Bridgers moved to Paris in 1947.

Strayhorn's arrival coincided with what many consider the Ellington orchestra's peak, the "Blanton-Webster" band that also included bassist Jimmy Blanton and tenor saxophonist Ben Webster. A 1940 dispute between ASCAP and the broadcasters kept Ellington's own catalog off the radio, and Strayhorn and Mercer Ellington, who were registered with ASCAP's rival BMI, helped write a fresh book for the band. "Take the 'A' Train," which Strayhorn is said to have composed in 1939 after Ellington sent him subway directions to Harlem, replaced "Sepia Panorama" as the theme; it was first recorded on January 15, 1941, for radio transcription, and the commercial recording of February 15, 1941, with a Ray Nance trumpet solo, became the band's signature. In the same years came "Raincheck," "Chelsea Bridge" and "A Flower Is a Lovesome Thing" (all 1941), "After All" and "Johnny Come Lately" (1942), "My Little Brown Book" and "Passion Flower" (1944), and "Lotus Blossom" (1946), all credited to him alone. Others, among them "Something to Live For," "Day Dream" and "Just A-Sittin' and A-Rockin'," were credited jointly with Ellington, and his "Sugar Hill Penthouse" section of Black, Brown and Beige (1943) went unacknowledged. He was also a pianist whom his peers respected: in the 1940s he had a cutting contest with Bud Powell, and Dizzy Gillespie, who watched, said Strayhorn turned the piano inside out; Max Roach recalled that after Strayhorn played at Minton's Playhouse nobody would follow him to the keyboard. "Lush Life" itself, which he said he wrote in 1936 while clerking in a Pittsburgh drugstore, had its first public performance on November 13, 1948, at Carnegie Hall, with Strayhorn and the vocalist Kay Davis appearing with the Ellington orchestra.

The 1950s brought larger forms. In 1950 Strayhorn helped Ellington prepare the extended concert arrangements of "Mood Indigo," "Sophisticated Lady" and "(In My) Solitude" for the LP Masterpieces by Ellington, without credit, and the same year the two recorded a set of piano duets for Mercer Records, later issued as Great Times! He is credited as co-composer of A Drum Is a Woman (1956), Such Sweet Thunder (1957), the Shakespeare suite whose pieces were written in under three weeks after the pair visited the Stratford, Ontario, festival in August 1956, and The Perfume Suite (1957). In the early 1950s he fleshed out an Ellington riff into "Satin Doll," adding harmony and a lyric that was later replaced by Johnny Mercer's. In 1956 he supervised the vocal overdubs in Los Angeles for Rosemary Clooney's Blue Rose, built on Ellington Orchestra backing tracks cut in New York. Away from Ellington he made some solo records, wrote revues for the New York social club the Copasetics, collaborated on theater projects with Luther Henderson, and wrote songs for Lena Horne, whom he coached on technique and who regarded him as the love of her life. Under his own name came Cue for Saxophone (Felsted, 1959; recorded April 14, 1959), a septet date that was really a Johnny Hodges session, issued under Strayhorn's name because Hodges was contracted to Verve and credited as "Cue Porter," and !!!Live!!!, a 1958 Ellington orchestra concert from Chicago's Blue Note club that Roulette originally released under Strayhorn's name.

He and Ellington scored Anatomy of a Murder (1959), regarded as the first significant Hollywood score by Black composers to use non-diegetic music, and arranged The Nutcracker Suite (1960) for Columbia, whose cover carried Strayhorn's name and picture beside Ellington's. In Paris in 1961 for the film Paris Blues, where "Take the 'A' Train" plays over the opening and Strayhorn went uncredited, he recorded The Peaceful Side in May at Barclay Studios, ten of his pieces for solo piano, bass, string quartet and a wordless vocal group, released in 1963 by United Artists Jazz. In December 1961 he arranged and conducted Johnny Hodges with Billy Strayhorn and the Orchestra (Verve, released 1962), with Jimmy Jones at the piano. A friend of Martin Luther King Jr. and an active supporter of the civil rights movement, he arranged and conducted "King Fit the Battle of Alabam'" for the 1963 revue and album My People. He was open about being gay among friends and the members of the band.

In June 1965 he gave the only concert of his career as a leader, to a sold-out house in the 450-seat New School auditorium in New York, presented by the Duke Ellington Jazz Society: a solo piano set, a trio set with bassist Wendell Marshall and drummer Dave Bailey, and a small-group set with Ellington sidemen including Clark Terry. Pianist Randy Weston, in the audience, said Strayhorn blew the hall away, and Dan Morgenstern praised the performance in DownBeat. His last recordings as a leader, made between January 1964 and August 1965, include small-group dates, accompaniment of the singer Ozzie Bailey and solo piano, and were collected in 1992 as Lush Life on Red Baron. He and Ellington finished the Far East Suite in December 1966 while his health declined; esophageal cancer had been diagnosed in 1964, and he submitted his last composition, "Blood Count," from the hospital. Strayhorn passed away in New York City on May 31, 1967, at fifty-one, with his partner Bill Grove at his side, and his ashes were scattered in the Hudson River by close friends. Ellington's memorial album ...And His Mother Called Him Bill, recorded between August 28 and November 15, 1967, is built from Strayhorn's compositions and ends with Ellington alone at the piano playing "Lotus Blossom" as the band packs up in the background.

Strayhorn was inducted into the Songwriters Hall of Fame in 1984, shared a Grammy Trustees Award with Ellington in 1968, and entered the International Society of Jazz Arrangers and Composers Hall of Fame in 2021. The Ellington orchestra's 1941 recording of "Take the 'A' Train" is in the Grammy Hall of Fame (1976). A historical marker stands at Westinghouse High School and another in Hillsborough, and Pittsburgh's former Regent Theater was renamed the Kelly Strayhorn Theater in 2000, in honor of Strayhorn and Gene Kelly. He joined Chicago's Legacy Walk in 2015 and was named to the 2026 class of the North Carolina Music Hall of Fame. In October 2026 Reservoir Media announced that it had acquired his publishing catalogue.

Strayhorn brought a classical composer's training in harmony and orchestration into the Duke Ellington band, studying the leader's scores until he had cracked what he called the "Ellington effect," so thoroughly that Gunther Schuller wrote it is often impossible to say where one man's work ends and the other's begins. His own pieces keep a bittersweet, introspective cast: "Lush Life," with its long verse and chromatic harmony, is an art song more than a pop tune, and "Chelsea Bridge" and "Blood Count" show the same mix of lush voicings and restraint. He said he wrote "Take the 'A' Train" with the brass-and-reed writing of Fletcher Henderson in mind. As a pianist he favored spare, formally shaped lines at slow tempos, and he was a trusted accompanist and arranger for singers and for the Ellington small groups. Fred Hersch called him a quadruple threat as composer, pianist, songwriter and arranger for jazz orchestra. His songs have been interpreted by John Coltrane and Johnny Hartman ("Lush Life," 1963), Stan Getz (seven recordings of "Blood Count"), Joe Henderson (the 1992 album Lush Life: The Music of Billy Strayhorn), Art Farmer (Something to Live For, 1987), Hersch (Passion Flower, 1996) and Jimmy Rowles (Jimmy Rowles Plays Duke Ellington and Billy Strayhorn, 1981), among many others. His reputation, long overshadowed by Ellington's, rose in the 1990s, helped by David Hajdu's 1996 biography Lush Life, and his role in the Ellington repertoire is now credited far more fully.