Portugal was not directly involved in World War II, but had to defend its neutrality. The War caught the AM in the beginning of a modernization plan that could not proceed due to the start of the conflict, meaning that it largely lacked modern aircraft. One of the major Portuguese military priorities became the deterrence of a possible invasion of the strategic Azores Islands, which were coveted both by the Axis and by the Allies, with both having plans to invade them. Adolf Hitler wanted to used the Azores as the base for the Amerika Bomber, with their seizure being included in the German planned operations Felix, Ilona and Isabella. The Allies wanted to use the Azores as an air and naval base to control the North Atlantic in the scope of the Battle of the Atlantic, having plans to invade them if the Portuguese Government refused to cede its use. This invasion was part of the planned British operations Alloy, Shrapnell, Brisk, Thruster, Springboard and Lifebelt and of the US Operation Grey. Faced with the imminent danger, the Portuguese authorities decide to reinforce the Azores garrison, sending to there a great part of the available Army forces and most of the AM combat aircraft, including all its fighters. In June 1941, two expeditionary fighter flights - each with 15 Gloster Gladiators- are organized and deployed, as well as five Ju 52 bombers. One of the fighter flights and the bombers became based at Santana airfield (Rabo de Peixe), São Miguel Island and the other fighter flight became based at Achada airfield, Terceira Island (sooner transferred to the newly built Lajes airfield). In October 1941, the AM receives Curtiss 75 Mohawk fighters, with 12 forming a third expeditionary fighter flight to the Azores, being stationed at Rabo de Peixe. In 1942, the Rabo de Peixe and the Lajes airfields became, respectively, the No 4 and No 5 air bases.

The sending of all the few available AM fighters to the Azores meant that Mainland Portugal remained without air defense. This issue will be gradually solved from 1943, thanks to the good relations of the Portuguese authorities with the Allies and the grant of air facilities at Lajes for the operation of anti-submarine aircraft. The AM starts then to receive modern fighters including Bell P-39 Airacobra, Hawker Hurricane, Supermarine Spitfire and Bristol Blenheim bombers (which replaced the Junkers Ju 86). The fighter and bomber flights that are formed with them are identified by a two-letter code that is painted on the fuselages. By the end of the World War II, the AM included the BA1, Sintra as a training unit, the BA2, Tancos with fighter flights MR (Spitfire), RL (Spitfire), XZ (Spitfire) and OK (Airacobra) and with bomber flight ZE (Blenheim), the BA3, Ota with Information and Reconnaissance Group (Westland Lysander) and Fighter Flight GL (Hurricane), BA4, Rabo de Peixe, with expeditionary fighter flights No 1 (Gloster Gladiator) and No 2 (Mohawk) and with the Ju 52 flight (used mainly in the air transport between Azores islands), BA5, Lajes with Expeditionary Fighter Flight No 2 (Gloster Gladiator), Lisbon Field with Fighter Flight VX (Hurricane) and Transport Aircraft Section (Consolidated B-24 Liberator, Lockheed Hudson and Douglas C-47) and Espinho airfield with Fighter Flight RV (Hurricane). The Lajes Air Base largely contributed for the Allied victory in Europe, first in its use by the British Royal Air Force in the elimination of the German submarine threat in the North Atlantic and then in its use by the United States Army Air Force (USAAF) in the air connection between the USA and Europe and North Africa, enable it to reduce the time of flight and largely increase the number of logistic flights that were able to supply the troops fighting the Axis.

Already after the War, by the Ordinance 12194 of 19 December 1947, the AM suffers its last major re-adjustment of its units still under the Army tutelage. As part of this, the BA4 (Santana Air Base) was disbanded, with its aeronautical facilities being transferred to the Ministry of Communications to become the civil airport of São Miguel Island. With this disbandment, Lajes was re-designated "No 4 Air Base (BA4)". By this time, Lajes was already one of the major air bases of the AM, including the longest runway in the world and well developed support facilities that included a seaport and a military hospital. From 1945, it was open to the civil air traffic, serving so as the civil airport of the Terceira island. The AM activities carried way from Lajes become increasingly focused in the maritime search and rescue operations, using Boeing SB-17 Flying Fortress and Douglas C-54 Skymaster aircraft. Since 1944, its main user had become however not the Portuguese aviation, but the USAAF. Besides its importance for the Allied victory in World War II, Lajes would continue to be strategically crucial for the US Military in future conflicts, especially in the Cold War, Berlin airlift, Yom Kippur War and Gulf War. In the scope of the re-organization of 1947, the Monte Real airfield (future Monte Real Air Base) - at that time was under construction - became dependent from the BA1, Sintra.

Portugal joined NATO in 1949 as one of its founders. With this joining, the AM increasingly comes under the influence of the US air forces, adopting many of its standards.