The 4th Infantry, Missouri National Guard was organized on 1 March 1891 with companies at Brookfield, Mound City, Linneus, Bethany, Richmond, St. Joseph, and Savannah.

The regiment was mustered out at Camp Wetherill, South Carolina on 10 February 1899 and returned to state status.

The 4th Missouri was mustered in to federal service on 26 June 1916 for duty on the Mexican border and stationed at Laredo, Texas.

It was mustered out on 28 February 1917 at Fort Riley, and drafted into federal service on 5 August 1917 at Nevada, Missouri.

In the 1990s, North Carolina's Officer Candidate School (OCS) was rebranded as the 139th Regional Training Institute (RTI) at Fort Bragg, reusing the heraldry of the regiment.