Born to a middle class Jewish family in Vienna, Zeisl's musical precocity enabled him to gain a place at the Vienna State Academy (against the wishes of his family) when he was 14, at which age his first song was published. He won a state prize for a setting of the Requiem mass in 1934, but his Jewish background made it difficult to obtain work and publication. After the Anschluss in 1938 he fled, first to Paris, where he began work on an opera based on Joseph Roth's Hiob (in English Job), and then to New York.
Eventually he went to Hollywood where he worked on film music but increasingly felt isolated and ill at ease with the production-line demands of his employers. Among the films for which he wrote music were Lassie Come Home (1943), The Postman Always Rings Twice (1946), and Abbott and Costello Meet the Invisible Man (1951).
Zeisl's style was essentially tonal, and conservative compared to contemporaries such as Arnold Schoenberg, and thus not totally unsuited to film music composition. But his heart lay elsewhere. At one stage he was employed to arrange the music for a highly inaccurate stage show about the life of Tchaikovsky, Song without Words. His anguish about his reduction to such work (together with the straits to which other emigre composers in America were reduced at the time) is evident in a letter written to a friend in 1945:
'Even Milhaud, Stravinsky, Tansman are struggling. Bela Bartok died in New York of hunger! [...] Last year I orchestrated a Tchaikowsky operetta which provided [a] living for 8 months, but why does Tchaikowsky have to be put into an operetta? [...] No composer is important here'.
Nonetheless Zeisl was able eventually to find academic appointments and time to compose in his own style. These works included a variety of chamber music, a piano concerto, a concerto for cello (written for Gregor Piatigorsky), and a setting for choir, soloists, and orchestra of Psalm 92 in Hebrew, which he entitled Requiem Ebraico ("Hebrew Requiem"), written in 1944-5 in memory of his father. His opera Hiob was never completed.
Zeisl died of a heart attack while teaching in Los Angeles.