He worked as a writer and editor for every major journal of the inter-war era, and was the founder and editor of the journal Globus, which during its short existence was one of the most important forums for literary and political debate.

A polyglot scholar of both Jewish and secular knowledge, Tseytlin was a tireless exponent of higher Yiddish and Jewish literature. He wrote extensively on God, the Jewish people, Israel, the Holocaust and a host of other topics; his collected essays are a masterwork of cogent and philosophically substantive Yiddish prose. His poetry is a distillate and expansion of the Jewish struggle with God. Though Tseytlin was not observant in the traditional sense, he is one of the most important Jewish religious writers.

Tseytlin came to New York in 1939 in order to supervise the production of one of his plays. He was a major figure in Jewish cultural life, and was professor of Hebrew literature at the Jewish Theological Seminary in New York. He died in 1973 and was buried in Israel.