Malmstrom AFB is one of many air bases dating to the US buildup to World War Two. Planning and funding for a base near Great Falls, Montana, as early as 1939, but site selection waited until 1940 and construction until spring of 1942. The base, Great Falls Army Air Base, was functional before the end of summer, and assigned the mission of providing air route support for materiel airlifted to the Soviet Union, in the Lend-Lease program supporting the war against the invading German Army (this air route channeled across the Pacific Northwest, Western Canada, and Alaska to the Soviet Far East). By fall, Great Falls AAB was assigned bomber training for the B-17 Flying Fortress; these units were assigned to the air war over Europe.

B-17 training continued through late 1943, when Great Falls AAB was transferred to Air Transport Command (now Air Mobility Command) for concentrated air ferrying mission focus. Over the course of the war over 1.7 million pounds of materiel, from tools to explosives to medical supplies, were shipped to Soviet allies through Great Falls alone, along with over 8,000 aircraft.

The end of the war brought a reduction in military preparedness, but Great Falls AAB continued operations as a support base for Alaskan military installations and other air supply missions worldwide. Tension between the US and USSR led to the Cold War and division of Europe; soon the Soviet Union blockaded ground routes into Berlin in order to claim the entire city as part of East Germany. Units from the newly renamed Great Falls Air Force Base flew air supply missions to the people of Berlin as part of 1948's Operation Vittles, transporting food, fuel, and other vital supplies on C-54 Skymasters. Great Falls AFB itself was the training center for this operation, having transformed its runways into a mockup of Tempelhof Airport for flight training, using radio beacon and runway light patterns.

Great Falls AFB continued its airlift support mission through the Korean War, scheduling and routing supply flights. Great Falls AFB was also the temporary home base of the 582d Air Resupply and Communications Wing, specializing in intelligence operation agent air infiltration and exfiltration.

By the middle of the 1950s Great Falls was renamed Malmstrom Air Force Base, after Colonel Einar Axel Malmstrom, once vice wing commander at Great Falls AFB, and combat veteran of World War Two. Col. Malmstrom had endeared himself to the local Great Falls, and after his death near the base a petition to rename the base for him was forwarded.

Malmstrom was reassigned to Central Air Defense Force about the same time, beginning a long base association with air defense against expected attack from the north. Later in the 1950s Malmstrom began to convert from bomber base support to missile basing, installing and housing Minuteman I ICBMs, under the 341st Strategic Missile Wing. These missiles were installed from 1961 to 1963; even before full installation the Minuteman missiles were operational, and in 1962 went on full alert during the Cuban Missile Crisis, responding to Soviet aggressive maneuvers worldwide. President John Kennedy referred to missiles at Malmstrom as his "Ace in the Hole" in dealing with and resolving the Crisis, and for the next 25 years Malmstrom's missiles continued at central role as a nuclear deterrent.

The Cold War ended in the late 1980s, leading to a broad realignment of US armed forces. Over the next several years the US nuclear arsenal was reduced and consolidated, with Malmstrom becoming one of three primary bases for strategic nuclear weapons. In the same wave of adjustments the last fixed wing units at Malmstrom was transferred to another base and the main runway closed.

Today, Malmstrom AFB remains a key strategic forces facility, housing modern Minuteman III ICBMs.