Dozens of variants of the C-54 were employed in a wide variety of non-combat roles such as air-sea rescue, scientific and military research, and missile tracking and recovery.

With the looming entry of the United States into World War II, in June 1941[citation needed] the War Department took over the provision orders for the airlines for the Douglas DC-4 and allocated them to the United States Army Air Forces with the designation C-54 Skymaster.

[1] To meet military requirements, the first civil production aircraft had four additional auxiliary fuel tanks in the main cabin, which reduced the number of passenger seats to 26.

The following batch of aircraft, designated C-54A, were built with a stronger floor and a cargo door with a hoist and winch.

By January 1946, Pan American Airways was operating their Skymasters on transatlantic scheduled services to Europe and beyond.

[6] On 3 July 1947, US Army Air Forces C-54G 45-519 crashed in the Atlantic 294 mi off Florida after a loss of control caused by turbulence from a storm, killing the six crew.

[7] On 14 May 1948, an army transport plane flying through a rainstorm crashed in Northampton, Massachusetts, killing the three crew members aboard.

[11] On 19 September 1950, a U.S. Navy C-54 en route to Korea crashed into the sea approximately one minute after takeoff from Kwajalein Atoll, Marshall Islands.

[13] On 29 April 1952, an Air France Douglas C-54A (registration F-BELI) operating a scheduled service from Frankfurt Rhein-Main Airport to Berlin Tempelhof Airport came under sustained attack from two Soviet MiG-15 fighters while passing through one of the Allied air corridors over East Germany.

[14] On 23 July 1954, a Douglas C-54 Skymaster civilian airliner, registration VR-HEU, operated by Cathay Pacific Airways, en route from Bangkok to Hong Kong, was shot and heavily damaged by Chinese PLAAF Lavochkin La-11 fighters off the coast of Hainan Island.

The crash occurred at roughly 8:30am during a high wind snowstorm with limited visibility approximately 35 miles northwest of Las Vegas.

The airplane was en route to a classified destination referred to as "Watertown" (now known as the Area 51 test site in Nevada) from Burbank, California.

Flying from Wheelus Field in Tripoli to Casablanca, it was believed en route to the United States.

Eight United States airmen died when their plane exploded in the rugged Riff Mountains of North Africa.

[21] Data from McDonnell Douglas aircraft since 1920 : Volume I[22]General characteristics Performance A C-54, registration C-FIQM (Buffalo 5-721 (tail 57)), was used as a substitute Lancaster bomber due to its similar top speed and maximum payload, for a recreation of Operation Chastise with its bouncing bomb.