The 21st Fighter Group (FG), activated on 21 April 1944 at Wheeler Air Field in what was then the territory of Hawaii. Assigned to VII Fighter Command, the group consisted of the 46th, 72nd and 531st Fighter Squadrons.

Over the next two months, the group trained on its first aircraft type, the P-39Q Airacobra. The 21st provided air defense over the Hawaiian Islands from July 1944, then began upgrading into the P-38J/L Lightning in September. By the end of October, rumors filled the air that the group soon would upgrade airframes again, this time to the P-51 Mustang. This change in aircraft heralded a new mission for the 21st FG.

True to rumor, leading echelons began deploying by ship to the island of Iwo Jima in the western Pacific in February 1945. Before the end of the month, the 21st began flying patrols over the critical island base in support of ground operations.

The final group echelon arrived at Iwo Jima on March 25. Early the next morning, elements of the 21st were attacked in their encampment by Japanese soldiers. Assisted by a patrol of American Marines, 21st personnel counter-attacked and in the tent-by-tent fighting killed 250 of the enemy. Fourteen group personnel were killed and 50, including 21st FG commander Colonel Kenneth Powell, were wounded.

The first long-range aerial mission of the 21st Fighter Group against the mainland of Japan began on 7 April 1945, when the group's Mustangs escorted a formation of B-29 bombers against the fortified and well defended Nakajima aircraft factory near Tokyo. This mission marked the first time fighters had escorted bombers over Japan. Moreover, this mission has been credited as having been the longest over-water fighter escort sortie to date. Over the following weeks, the 21st escorted American B-29s over enemy airfields and industrial targets and engaged rival Japanese fighter aircraft.

The 531st Squadron achieved another first for the 21st FG in June 1945 by initiating aerial rocket strike sorties against select enemy targets which included ships and a radio station.

In the meantime, the group's aircraft continued to duel in the air and two "aces" soon emerged-Major Harry Crim and Captain Willis Matthews, both of the 531st Fighter Squadron. Aircrews of the 21st also strafed the airfields which the Japanese used for their increasingly dangerous kamikaze attacks.

The 21st FG flew its last combat mission 14 August 1945, about two weeks before the official Japanese capitulation on 2 September. The group received the Distinguished Unit Citation on 13 November 1945 specifically for its outstanding conduct during the earlier raid on Nakajima. However, the 21st had played a laudable part throughout the final stages of the war in the Pacific.

After the war, the group transferred from Iwo Jima, first to Saipan, then finally to Guam. The original 21st FG inactivated on 10 October 1946.