He served as a Confederate cavalry general during the American Civil War, in which he was wounded twice, and fought mainly in the Western Theater of the conflict.

Because his father had lost his fortune, William Humes needed to borrow money to finish his initial education.

[5] Humes was posted to the Confederate fortifications protecting the Mississippi River near New Madrid, and was given command of the artillery guns there.

[7] On March 15, 1863, Humes was promoted to the rank of major and assigned to command the artillery of Maj. Gen. Joseph Wheeler's cavalry corps.

[12] He then resisted Sherman's March to the Sea in late 1864, and fought during the Battle of Buck Head Creek on November 28.

Near the end of the American Civil War, Humes surrendered with Gen. Joseph E. Johnston on April 26, although there is no record of an individual parole or pardon.