The airport was originally built in 1942 by the United States Army Air Forces as a training base for Air Corps Flying Training Command. Gulfport Army Airfield opened on July 7, and the Eastern Technical Training Command conducted technical training and basic training unit transferred to Third Air Force on March 31, 1944 with joint use by Technical Training Command for marine training of Emergency Rescue School (3d Air Rescue Group) at Keesler Army Airfield. With the end of the war and the drawdown of the military, Gulfport AAF was placed into reserve status on January 31, 1946.

Gulfport Field was declared excess by the Air Force and conveyed by the War Assets Administration to the City of Gulfport in 1949 for use as a civil airport. The city negotiated airline service contracts with Southern Airways and later National Airlines to provide passenger and cargo service beginning in the early 1950s.

Due to the large expansion of the United States Air Force as a result of the Cold War, a new lease was obtained for military use of the airport, and Gulfport Air Force Base was opened as a joint-use civil–military facility. Gulfport AFB was closed as an active Air Force installation and its military facilities were transferred to the Mississippi Air National Guard, with the airport remaining a joint-use airport and Air National Guard base. Although no military aircraft are permanently assigned, the base serves as the home of the Gulfport Combat Readiness Training Center.

Through the late 1970s, Southern Airways continued as the primary airline, followed by successors Republic Airlines and Northwest Airlines into the 1990s.