Some years before the start of World War I, the Mayo brothers had enlisted in the Reserves and had been commissioned first lieutenants in the Medical Reserve Corps. Despite their expectations, neither Mayo served in France during World War I.
Instead, both initially served on the General Medical Board of the United States Council for National Defense shortly after it was formed in 1916 to prepare America for possible military action. After the U.S. declaration of war in April 1917, Dr. William C. Gorgas, Surgeon General of the U.S. Army, asked Dr. Will to be a surgical consultant in his office in the nation's capital. Under Dr. Will's direction, a team of surgical experts was formed, which included both Mayo brothers. They alternated their military duty in the Surgeon General's office. That way, one brother could always be at the clinic to care for patients. In this way, the Mayo brothers served their country and fulfilled their duties to Mayo Clinic.
In 1921, they were both commissioned brigadier generals in the Medical Reserve Corps of the U.S. Army. In March 1926, the Mayo brothers were honored for their wartime efforts with the Distinguished Service Medal of the United States.