In 1916 he was appointed instructor and assistant professor of politics at Western Reserve University and from 1919 was director of the Cleveland Foundation.

He joined the Barnard College faculty in 1923, then became a professor of law at Columbia University from 1928–1954, where he was a specialist on the criminal justice system.

Despite ridicule from editorial and political cartoonists, the "Brain Trust" went to Washington and became powerful figures in Roosevelt's New Deal, with Moley writing important speeches for the president.

"[4] In mid-1933 Moley began his break with Roosevelt, and although he continued to write speeches for the president until 1936, he became increasingly critical of his policies, eventually becoming a conservative Republican.

However he was also a trenchant critic of fascism, as his participation in a March 1934 mock-trial event in New York City condemning Nazi Germany, titled “The Case of Civilization Against Hitler,” indicates.