He was born in Cambridge, across the river from Boston, and worked in that region until he came to New York in the mid-1920s. He played both alto and soprano sax, having had a few lessons from Sidney Bechet on the latter instrument. He was always capable of playing soprano in a style strongly derivative of Bechet's, but he chose to specialise on the alto from the time he joined Chick Webb's band in the mid-20s.
Ellington liked Hodges' strongly identifiable sound, and wrote many pieces to feature the taciturn-looking altoist. He also involved Hodges in the many small group recording sessions that he made with members of the orchestra, giving him the chance to play more extended solos. He also played on many freelance sessions, notably with Lionel Hampton.
Hodges had several nicknames, of which the best-known were Rabbit and Jeep, the latter commemorated by Ellington in two pieces that contrasted the altoist's main skills - his mastery of slow tempos on Jeep's Blues, and the jaunty swinging Jeep Is Jumping. Between them, Ellington and his co-composer Billy Strayhorn write many more features for Hodges, including the delicate ballads Passion Flower and Isfahan (from the Far East Suite). Hodges died during the recording sessions for Ellington's New Orleans Suite, and his final disc was the rousing Blues For New Orleans.