Frank Comerford Walker was born May 30, 1886, in Plymouth, Pennsylvania. He attended Gonzaga University in Spokane, Washington, for three years and received a law degree from Notre Dame University in Indiana (1909). Walker began his career in a law practice with his older brother Thomas and served a single term in the Montana State Legislature (1913).During World War I, he volunteered as a first lieutenant for the U.S. Army and saw limited action on the western front before returning to his law practice in Butte, Montana. In 1925, he moved to New York to become general counsel and manager of Comerford Theatres. In 1931, Walker became a founding member of the Roosevelt for President Society.

President Roosevelt named him treasurer of the Democratic National Committee in 1932, and Walker was subsequently appointed to the president's emergency council, later renamed the National Emergency Council, as executive secretary (1933-1935). He entered the Roosevelt cabinet in 1940, serving as postmaster general until 1945.

After resigning that July to allow the new President to appoint his own postmaster general, Walker was named an alternate delegate to the first United Nations General Assembly meeting in December 1945. He died on September 13, 1959, in New York City.