It was organized at Lockbourne Army Airfield, Columbus, Ohio, and was extended federal recognition on 10 November 1947 by the National Guard Bureau.

The squadron was equipped with F-51D Mustangs and was assigned initially to the Illinois ANG 66th Fighter Wing, operationally gained by Continental Air Command.

Parts were no problem and many of the maintenance personnel were World War II veterans so readiness was quite high and the planes were often much better maintained than their USAF counterparts.

With the surprise invasion of South Korea on 25 June 1950, and the regular military's complete lack of readiness, most of the Air National Guard was called to active duty.

On 20 September, the 166th was reassigned to the Federalized Oregon ANG 142d Fighter-Interceptor Group which was headquartered at O'Hare International Airport with no change of mission.

However, ADC was experiencing difficulty under the existing wing base organizational structure in deploying its fighter squadrons to best advantage.

[2] However, Strategic Air Command (SAC) had taken over Lockbourne AFB on 1 April 1951 and it was decided to move the 166th to Youngstown Municipal Airport, Ohio, which was accomplished in August 1952.

The mission of the 7121st TW was tactical air support of US Army units in case of an armed conflict with the Warsaw Pact, and alert began almost immediately upon arrival.

Weather permitting, daily missions at U S Army training ranges in West Germany were also flown to exercise with ground units there.

In July 1962 the deployed Air National Guardsmen were no longer needed in Europe and the 7121st began to redeploy its personnel to Ohio.

During the mid-1960s the squadron trained with the supersonic jet, however on 26 January 1968, in response to the USS Pueblo incident, President Johnson mobilized a major portion of the Selected Reserve Force, which included the 166th TFS.

Along with the Kansas ANG F-100C 127th Tactical Fighter Squadron, the 166th was federalized and deployed to Kunsan Air Base, South Korea.

The performance of the ANG units at Kusan in 1968–69 suggested the prerequisites of effective air reserve programs and paved the way for adoption of the total force policy in 1970 which exists today.

In addition, the F-100's were slow in attaining altitude and lacked an effective all-weather, air-to-air combat capability, essential in Korea.

However the 121st TFW provided support for operations at home station while smaller elements and individuals served as active duty augmenters in several locations.

Stationed at Sheik Isa Air Base, Bahrain, it served under combat conditions, returning home in April 1991.

With the end of the Cold War, a major reorganization of the Air Force was soon underway which would bring about the most significant mission change in the history of the 121st.

Under the 120th ARW, the squadron began flying from bases in southern France to support strike aircraft during Operation Deny Flight missions over the Balkans.

After the terrorist attacks on 11 September 2001, the 121st Air Refueling Wing launched into immediate action supporting armed aircraft over the United States during Operation Noble Eagle.