Ordained a Baptist minister in 1903, he was a minister at Montclair, N.J. (1904–15), and taught at Union Theological Seminary (1908–46). In 1919 he became associate pastor at the First Presbyterian Church, New York City. Crowds filled the church to hear his sermons, but conservative Protestants denounced him as a “modernist.” His sermon “Shall the Fundamentalists Win?” (preached on May 21, 1922) caused an uproar and led to his resignation in 1925. Called to the Park Avenue Baptist Church within a few months, he requested construction of a larger, interdenominational church near Columbia University. Riverside Church was built with the aid of John D. Rockefeller, Jr., a trustee.

Fosdick was a prolific author of sermons, articles, and books. These include The Manhood of the Master (1913), The Secret of Victorious Living (1934), On Being a Real Person (1943), A Faith for Tough Times (1952), and The Living of These Days, an Autobiography (1956).