He was then appointed a second lieutenant in the Eleventh Regiment, United States Infantry and served until April 30, 1888, when he resigned to go into business as a civil engineer.

On May 20, 1898, he went on to serve with Troop C, New York Volunteer Cavalry (Brooklyn's Own) during the Spanish–American War in Puerto Rico, winning distinction.

He stayed on active duty and was promoted several times up to the rank of colonel, serving in the Quartermaster Corps until World War I.

While serving in France as quartermaster of the 1st Infantry Division, Clayton was killed during a German air raid on American trenches.

Their father, Henry DeLamar Clayton, Sr., was a prominent judge and major general in the Confederate army during the American Civil War and president of the University of Alabama.