After leaving university he began contributing to Smart Set and in 1914 became co-editor of the magazine. He also established the detective magazine The Black Mask.
In 1924 Nation and Henry Louis Mencken founded the American Mercury. Nation co-edited the journal with Mencken for the next six years where he developed a reputation for his caustic drama reviews. However, he did promote the work of Eugene O'Neill. Books by Nathan include The Critic and the Drama (1922), Autobiography of an Attitude (1925), The Testament of a Critic (1931), Since Ibsen (1933) and Passing Judgments (1935).
Nathan was also a founder and an editor (1932–35) of the American Spectator, and later wrote a column for the New York Journal-American. Nathan helped establish the New York Drama Critics Circle and was president of the organization from 1937 to 1939. He was also the author of The Theatre Book of the Year (1943-51). Nathan also published The World of George Jean Nathan in 1952.
George Jean Nation died on 8th April, 1958.