Keyes' next assignment was at the USMA, where he served as an instructor of French language. He was also head football coach for one season in 1917, compiling a record of 7–1.
In 1940, during World War II, Keyes was chief of staff of the 2nd Armored Division, which was then commanded by Major General George S. Patton who, like Keyes, was a fellow cavalryman who had served with distinction in World War I and had taken a significant interest in armored warfare. Patton was to think highly of Keyes, later stating that he "had the best tactical mind of any officer I know."
Keyes was originally serving as deputy commander of the Seventh Army during the campaign, once again serving under Patton, in July 1943. During Operation Husky, when Patton split the Seventh Army in half, Keyes was given command of the Provisional Corps, composed of the 2nd Armored Division, the 3rd Infantry Division and the 82nd Airborne Division, along with two United States Army Ranger battalions, and supporting units. Advancing 125 miles in five days, through difficult mountainous terrain, the corps captured most of Western Sicily, including Palermo, the Sicilian capital, along with some 53,000 Axis soldiers, mainly Italians, along with nearly 600 vehicles, in exchange for less than 300 casualties. The corps then settled down for garrison duties and the administration of western Sicily until it was disbanded on August 20, three days after the end of the campaign. For his actions in the brief Sicilian campaign Keyes was awarded the Army Distinguished Service Medal. General Dwight D. Eisenhower, the Supreme Allied Commander in the Mediterranean Theater of Operations (MTO) wrote to General George C. Marshall, the Chief of Staff of the United States Army, noting that his "reports on Keyes as an acting Corps Commander in the Sicilian affair was most favorable".
After the war Keyes commanded the Seventh Army from 8 September 1945 until its deactivation on 31 March 1946. In December 1945 he was by his friend George S. Patton's side when the latter died. This was followed by command of the United States Third Army, Patton's former command, from 1946 to 1947. In 1947, Keyes was appointed United States High Commissioner on the Allied Council for Austria. He served as Director, Weapons Systems Evaluation Group (WSEG) from 1951 to 1954.
Taaffe, Stephen R. (2013). Marshall and His Generals: U.S. Army Commanders in World War II. Lawrence, Kansas: University Press of Kansas. ISBN978-0-7006-1942-9. OCLC840162019.