Hook was born in New York to Jennie and Issac Hook. He earned his Bachelor's degree at the City College of New York in 1923, then his Master's and Ph.D. at Columbia University in 1927, where he was a student of John Dewey. Upon finishing his studies he was hired by New York University until his retirement in 1972. From 1948 to 1969 he was head of the department of philosophy, during which time he founded the New York University Institute of Philosophy.

At the beginning of his career, Hook achieved prominence as an expert on Karl Marx's philosophy and was himself a Marxist. He visited Moscow in the late 1920s and wrote enthusiastically about the Soviet Union. In 1932 he supported the Communist Party's William Z. Foster when he ran for President of the United States. However, he became critical of Stalin in the 1930s accusing him of prioritizing "the needs of the Russian state" over the needs of the international revolution. He broke completely with the Communist Party and Stalin over the Great Purge, supporting Leon Trotsky's efforts to clear his name in a special Commission of Inquiry led by Dewey, which investigated Stalinist charges against him made during the Moscow Trials.

During the Cold War he became a leading anti-Communist though he continued to consider himself a democratic socialist throughout his life. He believed that freedom of the press is not absolute and must yield on occasion to the nation's national security needs or to the rights of individuals.

In 1949, Hook founded Americans for Intellectual Freedom, the predecessor organization to the Congress for Cultural Freedom (CCF). Both were involved in covert propaganda activity, intended to dissuade American liberals or leftists from continuing to advocate cooperation with the Soviet Union, after the death of Franklin Delano Roosevelt. The CCF was funded through a variety of CIA fronts.

On May 23, 1985 Hook was awarded the Presidential Medal of Freedom by President Ronald Reagan.

Quotations
Religious tolerance has developed more as a consequence of the impotence of religions to impose their dogmas on each other than as a consequence of spiritual humility in the quest for understanding first and last things.

To deny me the right to err is therefore to deny me the right to believe.

Religious freedom in an open society has the best prospects of flourishing to the extent that it expresses itself as freedom of religious inquiry.

Religious tolerance has developed more as a consequence of the impotence of religions to impose their dogmas on each other than as a consequence of spiritual humility.