The wing's predecessor was the 454th Bombardment Group, activated in 1943 as a United States Army Air Forces combat organization.

It was discontinued six months later, when the 403d Troop Carrier Wing was released from active duty and assumed its mission, personnel and equipment.

Starting in 1960, one third of the wing's aircraft were maintained on fifteen-minute alert, fully fueled and ready for combat to reduce vulnerability to a Soviet missile strike.

[5] The 4228th (and later the 454th) continued to maintain an alert commitment until the 454th was inactivated except for periods when the wing's aircraft were deployed to support operations in Southeast Asia.

In 1962, the wing's bombers began to be equipped with the GAM-77 Hound Dog air-launched cruise missiles, The 4228th Airborne Missile Maintenance Squadron was activated in November to maintain these missiles In 1962, in order to perpetuate the lineage of many currently inactive bombardment units with illustrious World War II records, Headquarters SAC received authority from Headquarters USAF to discontinue its Major Command controlled (MAJCON) strategic wings that were equipped with combat aircraft and to activate Air Force controlled (AFCON) units, most of which were inactive at the time which could carry a lineage and history.

Under the Dual Deputate organization,[note 3] all flying and maintenance squadrons were directly assigned to the wing, so no operational group element was activated.

Once operationally ready with the B-52D, the 454th wing headquarters, staff, tactical aircraft and crews and maintenance personnel were integrated into SAC's combat forces in the Pacific and Southeast Asia.

Elements of the 454th Bombardment Wing completed more than 100 missions to South Vietnam without losing a single bomber to enemy aircraft fire.

By 1969 as the demand for pilots to support the war in Southeast Asia increased, the number of B-52s based stateside fell because they were needed overseas.