From 1908 to 1909, Kiesler studied at the Technische Hochschule in Vienna. From 1910–12, he attended painting and printmaking classes at the Akademie der bildenden Künste, both in Vienna. In July 1913, Kiesler quit the academy without having earned a diploma.

He married Stefanie (Stefi) Frischer (1896–1963) in 1920, and they moved to New York City in 1926, where he lived until his death. Kiesler collaborated there early on with the Surrealists, and with Marcel Duchamp. His writing was extensive, and his theoretical work embraced two lengthy manifestos, the article "Pseudo-Functionalism in Modern Architecture" (Partisan Review, July 1949) and the book Contemporary Art Applied to the Store and Its Display (New York: Brentano, 1930).

Stefi Kiesler died in September 1963. In 1964, the year before his death, Kiesler married Lillian Olinsey, his longtime secretary and confidante, as Stefi had advised him to do while she was still living. In May 1965, he traveled to Jerusalem for the inauguration of the Shrine of the Book; seven months later he died in New York City