VMF-221 was formed on July 11, 1941 in San Diego, California. In December of that year, following the attack on Pearl Harbor, they moved to Marine Corps Air Station Ewa in Hawaii. On December 25, 1941, fourteen Brewster F2A-3's landed on Midway Island after launching from the . They were originally part of a relief force bound for Wake Island, but were diverted to Midway instead after the force was controversially recalled on 22 December 1941, Wake Island fell on the following day. On March 1, 1942, VMF-221, VMF-222, VMSB-241, and their headquarters units formed Marine Aircraft Group 22 commanded by Lieutenant Colonel Ira L. Kimes.