The 539th FIS was activated in October 1943 at Westover Field, Chicopee, Mass. Shortly after activation, the squadron moved to Seymour Johnson Field, Goldsboro, North Carolina to become part of the 402nd Fighter Group where it operated under the Replacement Training Unit Program of the advanced phase of pilot training.

In December 1943, the squadron again moved, this time to Blethenthal Field, Wilmington, North Carolina, and was assigned to the 326th Fighter Group where it remained until disbanded in April 1944.

In January 1955 it received F-86D's and in August 1955 the unit designation was transferred to McGuire AFB as the 539th Fighter Interceptor Squadron where it received F-86L's.

In May 1959 the squadron transitioned to F-106A becoming the first squadron in the Air Defense Command to be equipped with the F-106's. The 539th was deactivated 31 Aug 1967.