In November 1941, VMF-211 flew 12 Wildcats aboard the USS Enterprise for movement to Wake Island, the scene of the squadron's heroic battle. On December 8, 1941 the Japanese attacked, destroying seven of the 12 aircraft on the ground. In the next two weeks, the remaining five planes repelled numerous attacks and inflicted great losses on the enemy. During the course of the defense, the Marine ground forces and VMF-211 caused the loss of at least four enemy warships, the first major Japanese naval vessels sunk during the Pacific war, and the squadron was credited with 8 aircraft destroyed. After the loss of its last aircraft, the squadron became a ground unit and fought until the surrender of atoll. The first Marine airman to be awarded the Medal of Honor in World War II was VMF-211's Henry T. Elrod. A planned operation to reinforce Wake Island was deemed too dangerous by the fleet command, and on December 25 Wake Island was finally overrun by a numerically superior enemy.
The squadron's rear echelon at Marine Corps Air Station Ewa lost all but one of its twelve F4F-3s during the attack on Pearl Harbor, and even this lone survivor was lost when it was transferred to the Navy. Slowly rebuilding as personnel and aircraft became available, the squadron, now under the command of Major Luther S. Moore was deployed in May 1942 to Palmyra Atoll in the South Pacific and adopted the name "Avengers" in memory of those squadron members who were killed or captured on Wake Island. When first deployed, VMF-211 was equipped with the Brewster F2A-3 and it was not until July that sufficient numbers of Grumman F4F-4 Wildcats became available to re-equip the squadron. As the Pacific Campaign continued the squadron transitioned to the F4U Corsair for the remainder of the war. VMF-211 participated in the Treasury-Bougainville Campaign, Battle of the Bismarck Sea, Northern Solomon, Battle of Leyte Gulf and Southern Philippine campaigns.