The book inspired Richard Strauss to compose the tone poem Also sprach Zarathustra, which he designated "freely based on Friedrich Nietzsche".
Zarathustra's Roundelay is set as part of Gustav Mahler's Third Symphony (1895–6), originally under the title What Man Tells Me, or alternatively What the Night Tells Me (Of Man).
Frederick Delius based his major choral-orchestral work A Mass of Life (1904–5) on texts from Thus Spoke Zarathustra. The work ends with a setting of Zarathustra's roundelay which Delius had composed earlier, in 1898, as a separate work. Another setting of the roundelay is one of the songs of Lukas Foss's Time Cycle for soprano and orchestra (1959–60).
Carl Orff also composed a three-movement setting of part of Nietzsche's text as a teenager, but this work remains unpublished.
Latin American writer Giannina Braschi wrote the philosophical novel United States of Banana based on Walter Kaufman's translation of Thus Spoke Zarathustra; in it, Zarathustra and Hamlet philosophize about the liberty of modern man in a capitalist society. Italian progressive rock band Museo Rosenbach released in 1973 the album Zarathustra, with lyrics referring to the book.