The 75th Fighter Squadron was first constituted as the 75th Pursuit Squadron (Interceptor) on 17 December 1941. On 15 May 1942, the squadron was redesignated as the 75th Fighter Squadron, and on 4 July 1942 it was activated into service flying P-40 Warhawks.

The 75th Fighter Squadron's first assignment as an active unit was in the China-Burma-India theater, where it absorbed members of the famous American Volunteer Group known as the "Flying Tigers." On the same day as its activation, the 75th scored its first major victory during a night interception flight against Japanese bombers. This was the first night interception ever attempted over the China theater and gave the Japanese quite a shock. The intercepting pilots were credited with the destruction of two enemy bombers and two probables.

During the early days of its history, the 75th's mission was to attack and destroy the enemy by strafing airfields, troops, and supply depots, while maintaining air superiority so that the Japanese could not locate and bomb targets in China. Operating from numerous airfields within China, the 75th Fighter Squadron compiled an impressive record during World War II and received the Presidential Unit Citation.

The squadron transitioned to the P-51 Mustang in 1944. The Tiger Sharks began flying the first "Thunderbolt", the P-47 in 1946. After the war the squadron returned to the United States and was stationed at Fort Lewis, Washington. The squadron was inactivated there on 5 January 1946. Following a period of activations and inactivations, during which the squadron was assigned to such bases as Northwest Field, Guam, and Howard Air Force Base, Canal Zone, the squadron returned to active duty on 12 January 1951 as the 75th Fighter-Interceptor Squadron stationed at Presque Isle Air Force Base, Maine. During this period, the 75th served under the Air Defense Command and flew the F-86 Sabre Jet with a mission to maintain a high degree of operational proficiency so that it might repel any possible enemy air attack. The squadron left Presque Isle on 16 October 1952 and was reassigned to Suffolk County Air Force Base, New York, where the squadron remained for three years before returning to Presque Isle.

The squadron continued to fly the F-86 until 1955 when it converted to the F-89. It continued operations out of Presque Isle until later moving to Dow Air Force Base, Maine.

In 1959 the squadron converted to the F-101, remaining at Dow Air Force Base until 1968 when it was transferred to Wurtsmith Air Force Base, Michigan. The squadron inactivated again on 30 November 1969.

On 18 May 1972, the squadron was redesignated the 75th Tactical Fighter Squadron, and on 1 July 1972 was activated at England Air Force Base, Louisiana. There the squadron began flying the A-7D "Corsair II" aircraft. The unit remained at England Air Force Base flying the A-7D until 1981 when conversion to the A-10 "Thunderbolt II" was completed.

On 18 November 1991, the 75th Tactical Fighter Squadron deactivated at England Air Force Base. On 3 April 1992, the squadron was again activated, this time under the "Flying Tiger" flag as the 75th Fighter Squadron located at Pope Air Force Base, North Carolina.

Since the move to Pope AFB, the Tiger Sharks have participated in contingency operations worldwide, including Operations UPHOLD DEMOCRACY, VIGILANT WARRIORS, NORTHERN WATCH, and SOUTHERN WATCH.

The Tiger Sharks closed out the summer of 2002 maintaining a 24-hour combat search and rescue alert posture at Ahmed Al Jaber, Kuwait for Operation SOUTHERN WATCH and around the clock close air support from Bagram Air Base, Afghanistan for Operation ENDURING FREEDOM. The 75th exceeded all execution expectations of the combat planners and directors. The Tiger Sharks were the only unit to never miss a combat alert or airborne close air support tasking, flying 665 combat sorties for a total of 1,836 flying hours.

The 75th is currently deployed for Operation IRAQI FREEDOM to Southwest Asia.