His father, Fletcher Hamilton Henderson (1857–1943), was the principal of the nearby Howard Normal Randolph School from 1880 until 1942.

At age 18, he moved to Atlanta, Georgia, and changed his name to Fletcher Henderson, giving up James, his grandfather's name.

[7] After graduation, Henderson moved to New York City with the intention of attending Columbia University for a master's degree in chemistry.

He did land a part-time job as a lab assistant in a downtown Manhattan chemistry firm, but this only lasted a year.

When Harry Pace left the company to start Black Swan Records, he took Henderson with him to be musical director, a job which lasted from 1921 until 1923.

On October 13, 1924, history was made when Henderson's band began their re-engagement at Roseland, with Armstrong now in the orchestra.

[4] Redman arranged Armstrong's repertoire with the King Oliver's Creole Jazz Band, such as turning "Dippermouth Blues" into "Sugar Foot Stomp".

[18] His band around 1925 included Armstrong, Howard Scott, Coleman Hawkins (who started with Henderson in 1923, playing the tuba parts on a bass saxophone, and quickly moving to tenor saxophone and a leading solo role), Charlie Dixon, Kaiser Marshall, Buster Bailey, Elmer Chambers, Charlie Green, and Ralph Escudero.

In 1925, with Henry Troy, he wrote "Gin House Blues", recorded by Bessie Smith and Nina Simone, among others.

[19] During the 1930s, he recorded for Columbia, Crown (as "Connie's Inn Orchestra"), ARC (Melotone, Perfect, Oriole, Vocalion), Bluebird, Victor, and Decca.

In addition to Armstrong, lead trumpeters included Henry "Red" Allen, Joe Smith, Rex Stewart, Tommy Ladnier, Doc Cheatham and Roy Eldridge.

Lead saxophonists included Coleman Hawkins, Buster Bailey, Benny Carter and Chu Berry.

Other jazz musicians who also played with Henderson included trumpeter Cootie Williams and trombonist Benny Morton.

Since Goodman needed new charts every week for the show, his brother-in-law John Hammond suggested that he purchase some from Henderson.

[21] The singer Helen Ward also stated that Henderson was delighted to hear the Goodman Orchestra realize his creations with such impeccable musicianship.

[4] He also played a key role in bringing improvisatory jazz styles from New Orleans and other areas of the country to New York, where they merged with a dance-band tradition that relied heavily on arrangements written out in musical notation.

Louis Metcalf said: "The sight of Fletcher Henderson's men playing behind music stands brought on a learning-to-read-music kick in Harlem which hadn't cared before it.