He worked odd jobs to earn enough money to buy his first piano, and took lessons from Charlotte Enty Catlin.

He played in the school band, and studied under Carl McVicker, who had also instructed Erroll Garner and Mary Lou Williams.

Strayhorn's fellow students, guitarist Bill Esch and drummer Mickey Scrima, also influenced his transition to jazz, and he began writing arrangements for Buddy Malone's Pittsburgh dance band after 1937.

Strayhorn worked for Ellington for the next 25 years as an arranger, composer, occasional pianist and collaborator until his death from cancer.

Ellington used Strayhorn to complete his thoughts and introduce new musical ideas (and sometimes it worked the other way around),[6] while giving him the freedom to write on his own and enjoy at least some credit.

"[8] Strayhorn composed the Duke Ellington orchestra's signature song, "Take the 'A' Train", and a number of other pieces that became part of the band's repertoire.

Strayhorn also arranged many of Ellington's band-within-a-band recordings and provided harmonic clarity and polish to Duke's compositions.

Detroit Free Press music critic Mark Stryker concludes that the work of Strayhorn and Ellington in the score of the 1959 Hollywood film Anatomy of a Murder is "indispensable, [although] ... too sketchy to rank in the top echelon among Ellington-Strayhorn masterpiece suites like Such Sweet Thunder and Far East Suite, but its most inspired moments are their equal.

In 1964, Strayhorn was diagnosed with esophageal cancer, which took his life in the early morning of May 31, 1967, when he was with his partner, Bill Grove, not in Lena Horne's arms as has often been falsely reported.

[1] The last track of the album is a solo version of "Lotus Blossom" performed by Ellington, who sat at the piano and played it while the band (who can be heard in the background) were packing up after the formal end of the recording session.

[20] A Pennsylvania state historical marker highlighting Strayhorn's accomplishments was placed at Westinghouse High School in Pittsburgh, from which he graduated.

[21] In North Carolina, a highway historical marker honoring Strayhorn is located in downtown Hillsborough, near his childhood home.