He had initially started his career writing in a neoclassical style, but gradually moved further towards more complex harmonies and postromanticism, and finally the twelve-tone serialism of the Second Viennese School.

Sessions' friendship with Arnold Schoenberg influenced this, but he would modify the technique to develop a unique style involving rows to supply melodic thematic material, while composing the subsidiary parts in a free and dissonant manner.

Graduating at age 18, he went on to study at Yale University under Horatio Parker and Ernest Bloch before teaching at Smith College.

With the exception, mostly, of his incidental music to the play The Black Maskers, composed in part in Cleveland in 1923, his first major compositions came while he was traveling Europe with his first wife in his mid-twenties and early thirties.

Sessions won a special Pulitzer Prize in 1974 citing "his life's work as a distinguished American composer.

The works from 1946 onwards are atonal and, beginning with the Solo Violin Sonata of 1953, serial although not consistently employing Viennese twelve-tone technique.