Hubert Work was born July 3, 1860, in Marion Center, Pennsylvania, and was educated at the University of Pennsylvania, where he obtained his M.D. in 1885. Work traveled to Colorado, where he established a medical practice and became involved in Republican Party politics. He became a representative from Colorado on the Republican National Committee in 1908, and a member of the State Republican National Committee in 1912.

During World War I, Work served in the Army Medical Corps as a colonel. Following the war, he was a delegate to the Republican National Convention (1920) and chair of the Republican National Committee (1928-1929). During that time, he was also president of the American Medical Association (1920).Work served President Warren G. Harding as postmaster general from 1922 to 1923, and as secretary of the interior in 1923. Following Harding's death, Work remained head of the interior department, resigning in 1928. During Work’s tenure in the cabinet, Native Americans were formally granted American citizenship. Hubert Work died on December 14, 1942, and was buried at Arlington National Cemetery.