The growing involvement of the United States military in World War II brought about the creation the 391st Tactical Fighter Squadron. On 24 May 1943, the Army constituted the 391st Fighter Squadron as part of the 366th Fighter Group. Both organizations existed only on paper until 1 June 1943, when the 366th Fighter Group and its three flying squadrons were activated at Richmond Army Air Base, Virginia. At Richmond, the new 391st Fighter Squadron received its personnel and equipment, beginning flight training in the P-47 Thunderbolt. Training continued after moving to Bluethenthal Air Field, North Carolina on 9 August 1943.
With initial training complete, the 366th Fighter Group entered the war in Europe with its arrival at Membury, England, on 10 January 1944, although the 391st did not complete the move until 2 days later. Here the squadron conducted theatre training, learning tactics used against the enemy from Allied pilots with combat experience. A move to Thruxton, England, took place on 2 March, with the squadron flying its first combat missions shortly thereafter.
Flying from England, the P-47s of the 391st Fighter Squadron conducted fighter sweeps over occupied Europe, bombing tactical targets as well as engaging Nazi planes in air-to-air combat. This general type of mission would continue throughout the war, which the 391st used in both air-to-ground and air-to-air roles. The squadron, as well as the entire 366th Group, supported action leading up to the Normandy invasion and flew many sorties during D-Day operations.
After the Allied forces gained a foothold on the Continent, the group and its squadrons earned a Distinguished Unit Citation supporting the St. Lo breakthrough. Aircraft of the 366th Fighter Group discovered and attacked a previously unidentified tank column heading toward the Allied lines, preventing an unexpected attack at this crucial phase of battle.
As the German Army was pushed back across Europe, the 391st changed bases several times. This allowed the fighters to penetrate behind enemy lines as the lines advanced toward Germany. In all, the squadron had three temporary bases in France, one in Belgium, and one in Germany itself before VE Day. After the Nazi surrender, the squadron remained in Germany as part of the occupation forces until inactivation on 20 August 1946.
The still inactive squadron received a new designation as the 391st Fighter-Bomber Squadron on 15 November 1952, with activation of the squadron occurring on 1 January 1953. The activation took place at Alexandria (later England) Air Force Base, Louisiana, with the squadron serving as a component of the newly activated 366th Fighter-Bomber Wing. While stationed at Alexandria/England AFB, the 391st flew the F-51 Mustang, F-84F Thunderstreak, F-86 Sabre, and the F-100 Super Sabre. Operations during the 1950's involved training, maintaining combat capability, and participating in various exercises. In the late 1950s, periodic rotations to Europe were added to this mission. The unit received a new designation as the 391st Tactical Fighter Squadron on 1 July 1958, with the wing re-designated the 366th Tactical Fighter Wing and the other flying squadrons getting similar names on the same date. Less than a year later, on 1 April 1959, the wing and its components again became inactivated.
After slightly over a year in France, the 391st Tactical Fighter Squadron and the rest of the wing returned to the United States and a new assignment at Holloman Air Force Base, New Mexico. Shortly after the 12 July 1963 arrival at Holloman, the squadron began converting from the old F-84 to the new F-4C Phantom II. With conversion complete, the unit concentrated on the normal peacetime operations of training and maintaining readiness until 26 January 1966, when the 391st Tactical Fighter Squadron was attached to the 12th Tactical Fighter Wing for operation control, although officially assigned to the 2nd Air Division and later the 7th Air Force. On 23 June, the squadron was finally assigned directly to the 12th Tactical Fighter Wing. While at Cam Rahn Bay, the unit took part in air-to-ground missions such as close air support and interdiction, as well as air-to-air operations such as rescue protection and combat air patrol.
On 22 July 1968, the 391st Tactical Fighter Squadron's direct involvement in the Vietnam conflict drew close with its reassignment to the 475th Tactical Fighter Wing at Misawa Air Base, Japan. Here the squadron mission changed to providing air defence to Japan. In addition, the 391st provided air defence to Korea through numerous deployments to Taegu Air Base and Kunsan Air Base in South Korea. This continued for almost three years, until the 1 July 1971 assignment of the squadron to the 347th Tactical Fighter Wing at Mountain Home Air Force Base, Idaho. This move took place without personnel or equipment, with the 391st Tactical Fighter Squadron designation moving to a squadron of F-111F aircraft at Mountain Home. The 366th Tactical Fighter Wing replaced the 347th Tactical Fighter Wing at Mountain Home on 31 October 1972, reuniting the 391st Tactical Fighter Squadron with its previous parent unit.
Squadron operations throughout the 1970s and 1980s centred on maintain combat capability and training F-111 aircrew. In 1977 Operation READY SWITCH brought a change in aircraft, with the F-111F fleet replaced by the older F-111A aircraft. After the conversion, the mission of the squadron remained relatively unchanged with the F-111 training and combat preparations continuing throughout the 1980s into 1990. The 391st Tactical Fighter Squadron ended its F-111A mission on 1 July 1990, with the squadron inactivated when the Air Force began to retire the F-111A fleet.
With the 366th Tactical Fighter Wing re-designated as the 366th Wing in preparation for a change to a composite force structure, the 391st once again became activated as a component of the wing. When activated on 11 March 1992, the squadron was re-designated as the 391st Fighter Squadron and equipped with the F-15E Strike Eagle, serving as a dual-role asset to the Air Force's first Air Intervention Composite Wing.