He studied law at the University of Prague and graduated in 1907 to work in the civil service. From 1924 he also worked as a critic for the Prager Tagblatt. From 1912 he was a pronounced Zionist and in 1918 he was made vice-president of the Jüdischen Nationalrats. In 1939 Brod and his wife emigrated to Palestine. He continued to write and also worked for Habimah, later the national theatre. He died in Tel-Aviv.
He is most famous as a friend of Franz Kafka, whom he first met in 1902. On Kafka's death in 1924 Brod was the administrator of the estate and preserved his unpublished works from incineration as stipulated in the will. Brod edited and later published Kafka's papers, and in 1937 wrote the first biography of his friend: Franz Kafka, eine Biographie.
Other published works by Brod include Tycho Brahes Weg zu Gott (1916), Heidentum, Christentum und Judentum (1922), Reubeni, Fürst der Juden (1925), Biografie von Heinrich Heine (1934), Rassentheorie und Judentum (1936), Franz Kafkas Glauben und Lehre (1948) and Verzweiflung und Erlösung im Werke Franz Kafkas (1959). He wrote extremely prolifically.
Brod's musical compositions are little known. They include songs, works for piano and incidental music for his plays. He translated some of Leos Janacek's operas, wrote a biography of him in 1924, and authored a study of Gustav Mahler, Beispiel einer Deutsch-Jüdischen Symbiose, in 1961.