The Soviet blockade of West Berlin began on 24 June 1948, and the Americans flew their first supply sorties two days later, at first with C-47s. The C-47 carried only about three tons, and the city needed thousands of tons a day. On 27 June more C-54s were ordered to Germany, and from July the Skymasters steadily took over; the last C-47s were withdrawn by the end of September.

In late July Major General William H. Tunner, who had run the Hump airlift in the Second World War, took command. His method was relentless standardisation. Aircraft flew in blocks at fixed heights and intervals so that faster and slower types did not mix, ground crews learned to load ten tons of coal into a C-54 in minutes, and turnaround times in Berlin were cut sharply. Air Force Magazine records a Fassberg-based C-54 completing a round trip in under two hours with a turnaround of only 15.5 minutes.

The climax was the Easter Parade of 16 April 1949, when in 24 hours the lift flew nearly 1,400 flights carrying about 12,900 tons. The Soviets lifted the blockade on 12 May 1949, but flights continued until 30 September. In all the Airlift delivered about 2.3 million tons in some 277,000 flights. The cost was more than 100 accidents and dozens of lives: Air Force Magazine gives 77 dead, 31 of them Americans.

In the Second World War the C-54 gave the United States its first truly global military air transport. Its range let it fly non-stop between the United States and the European and Pacific theatres, carrying high-priority cargo, staff and passengers out and casualties home. Navy R5Ds flew the same work across the Pacific, among them casualty evacuation from Okinawa. One specially built aircraft, the VC-54C Sacred Cow, served as the presidential aircraft of both Roosevelt and Truman.

Five years later the Skymaster was at war again. On 25 June 1950, the first day of the Korean War, North Korean fighters attacked Kimpo and destroyed a USAF C-54 on the ground. Over the next days C-54s and C-47s evacuated hundreds of American civilians from Korea to Japan, 748 on 27 June alone and 851 US citizens by air in all by 28 June, under fighter escort. The heavier C-54 was soon found to damage the rough runways at Pusan, but as the front moved, C-54s of Combat Cargo Command landed supplies at newly captured airfields such as Suwon. The Strategic Air Command museum credits them with evacuating some 66,000 patients back to the United States.

• C-54: the first batch, airliners commandeered on the Douglas line.
• C-54A / B / D: main wartime cargo and passenger versions; the D used R-2000-11 engines.
• C-54E / G: later versions with improved engines and fuel systems, able to switch quickly between cargo and passengers.
• VC-54C Sacred Cow: the presidential transport of Roosevelt and Truman.
• C-54M: Berlin Airlift-era coal carriers.
• R5D: US Navy and Marine Corps versions; some served in Antarctica with Operation Deep Freeze.
• HC-54 / EC-54U and others: post-war rescue and electronic versions.

Four 14-cylinder radials make the Skymaster expensive to keep in the air: fuel, oil and engine overhauls dominate. That is why the survivors that still fly are mostly operated by enthusiasts. The Berlin Airlift Historical Foundation in New Jersey, founded in 1988 by Timothy Chopp, flies its C-54 Spirit of Freedom as a flying museum and classroom on donations and volunteer labour. Others had long second careers as fire-fighting tankers: the Travis and March Field museum aircraft both worked as fire bombers before being retired to display.