During World War II, the 16th Squadron flew missions in New Guinea, India, and China in the Curtiss P-40 Warhawk, Republic P-47 Thunderbolt, and North American P-51 Mustang.

During the Korean War, the 16th Fighter-Interceptor Squadron flew missions from Korea and Japan in the Lockheed F-80 Shooting Star and North American F-86 Sabre.

After the Korean War, the 16th was stationed in Japan, Taiwan, Florida, Norway, Turkey, Korea, and Utah, flying missions in the Convair F-102 Delta Dagger and McDonnell F-4 Phantom II aircraft.

The squadron flew strafing, bombing, reconnaissance, and patrol missions in support of Allied ground troops during a Japanese offensive in northern Burma in 1943.

Was reequipped with North American P-51D Mustangs in 1945 to defend the eastern end of the route over the Hump, and to guard air bases in the Kunming area.

In the early 1960s, the Air Force was implementing Project Clearwater, an initiative to withdraw Convair F-102 Delta Daggers from overseas bases in order to reduce "gold flow" (negative foreign currency transactions).

Participated in numerous airpower demonstrations, provided close air support of Army troops during tactical exercises, and prepared for overseas deployments.

Moved to Hill Air Force Base, Utah, and received first production General Dynamics F-16A Fighting Falcon aircraft to be delivered to an operational squadron on 6 January 1979.