The Mission of the Missouri National Guard is "to provide trained and disciplined forces for domestic emergencies or as otherwise required by state law under the authority of the governor."

[6] The Missouri Air National Guard was established following World War II, in 1947.

While serving in combat, the unit set up and operated the Empire Range EPW camp.

The Missouri Guard was the first Enemy Prisoner of War (EPW) unit to deploy as part of the 400th MP Battalion.

Eventually it set up and operated the 301st EPW Camp, near the Saudi Arabian city of Hafar al-Batin (Hotel 301).

In January 2021, Governor Mike Parson activated the Missouri National Guard to help administer COVID-19 vaccinations.

[9] In June 2022, the 1138th Engineer Company (Sapper) participated in Exercise African Lion in Morocco as part of US Africa Command.