[2] He was raised with a brother, Curtis D. Wilbur, who served as the U.S. Secretary of the Navy under President Calvin Coolidge, and was a judge of the Supreme Court of California.

[4][5] While a freshman at his Stanford home, Wilbur met future President Herbert Hoover, who was drumming up business on campus for a local laundry.

[4] In 1916, he was chosen to serve as president of Stanford and continued in that position until 1943, including during his tenure as Secretary of the Interior.

During World War I, Wilbur served as a chief of the conservation division of the United States Food Administration.

"[3] Wilbur reorganized graduate education, established the Lower Division, introduced Independent Study, and regrouped academic departments within the Schools of the University.

In 1923, he was one of the doctors called in to consult when President Warren G. Harding fell ill in San Francisco, and was present at his deathbed.

On March 5, 1929, President Hoover nominated Wilbur as the U.S. Secretary of the Interior confirmed by the Senate, and assumed office the same day.

[5] As Interior Secretary, Wilbur addressed corruption in granting contracts for naval oil reserves, which had caused controversy during the Harding administration's Teapot Dome scandal.

[3] Wilbur took a particular interest in Native Americans while in office and reorganized the department's Bureau of Indian Affairs.

[3] After leaving the Department of the Interior in 1933, Wilbur became a vocal critic of Franklin D. Roosevelt's New Deal and was the leading champion of "rugged individualism".