As a young man, Hughes was an honor graduate of Brown University where he was a member of Delta Upsilon Fraternity. After Brown he attended the Harvard Law School, serving as the editor of the prestigious Harvard Law Review during his third and final year there.
Admitted to the bar in 1913, Hughes was secretary to New York Judge (and future Supreme Court of the United States Justice) Benjamin N. Cardozo from 1914 to 1916. In 1914 Hughes was married to the former Marjory Stuart. After practicing corporate law briefly, Hughes joined the United States Army as a private shortly after U.S. entry in to World War I. Serving in field artillery, he was eventually commissioned a second lieutenant. Upon returning from the war, Hughes resumed the practice of primarily corporate law. Hughes practiced in the firm founded by his father, Charles Evans Hughes, Sr., then known as Carter, Hughes & Cravath (now known as Hughes Hubbard & Reed).
Appointed Solicitor General by Herbert Hoover, Hughes was compelled to resign when Hoover nominated Hughes' father to be Chief Justice of the United States, in order to avoid conflict of interest. Hughes re-joined Carter, Hughes & Cravath. He also served on the board of directors of New York Life Insurance Company, 1930-1934. Hughes was the father of the noted historian and activist H. Stuart Hughes, and Charles Evans Hughes, III, an architect, and two daughters, Helen Hughes and Marjory Bruce Hughes.
Judge Learned Hand once observed that Charles Evans Hughes, Sr., was the greatest lawyer he had ever known, "except that his son was even greater."
He died of a brain tumor on January 21, 1950 and was buried at Woodlawn Cemetery in Bronx, New York.