The C-47 was vital to the success of many Allied campaigns, in particular, those at Guadalcanal and in the jungles of New Guinea and Burma, where the C-47 and its naval version, the R4D, made it possible for Allied troops to counter the mobility of the light-traveling Japanese Army. C-47s were used to airlift supplies to the encircled American forces during the Battle of Bastogne in Belgium. Possibly its most influential role in military aviation, however, was flying "The Hump" from India into China. The expertise gained flying "The Hump" was later used in the Berlin Airlift, in which the C-47 played a major role until the aircraft were replaced by Douglas C-54 Skymasters.

In Europe, the C-47 and a specialized paratroop variant, the C-53 Skytrooper, were used in vast numbers in the later stages of the war, particularly to tow gliders and drop paratroops. During the invasion of Sicily in July 1943, C-47s dropped 4,381 Allied paratroops. More than 50,000 paratroops were dropped by C-47s during the first few days of the D-Day campaign also known as the invasion of Normandy, France, in June 1944. In the Pacific War, with careful use of the island landing strips of the Pacific Ocean, C-47s were used for ferrying soldiers serving in the Pacific theater back to the United States.

About 2,000 C-47s (received under Lend-Lease) in British and Commonwealth service took the name "Dakota", possibly inspired by the acronym "DACoTA" for Douglas Aircraft Company Transport Aircraft.

The C-47 also earned the informal nickname "gooney bird" in the European theatre of operations. Other sources attribute this name to the first aircraft, a USMC R2D—the military version of the DC-2—being the first aircraft to land on Midway Island, previously home to the long-winged albatross known as the gooney bird which was native to Midway.
The United States Air Force's Strategic Air Command had Skytrains in service from 1946 to 1967. The US Air Force's 6th Special Operations Squadron was flying the C-47 until 2008.

With all of their aircraft and pilots having been part of the Indian Air Force prior to independence, both the Indian Air Force and Pakistan Air Force used C-47s to transport supplies to their soldiers fighting in the Indo-Pakistan War of 1947.

After World War II, thousands of surplus C-47s were converted to civilian airline use, some remaining in operation in 2012, as well as being used as private aircraft.

In October 1956, a U.S. Navy R4D-5L named Que Sera Sera landed at the South Pole in Antarctica. This was the first time humans had been at the pole since 1912 (see Robert F. Scott's

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C-47 Initial military version of the DC-3 had four crew (pilot, co-pilot, navigator, and radio operator) and seats for 27 troops alongside the fuselage interior. "Aerial Ambulances" fitted for casualty evacuation could carry 18 stretcher cases and a medical crew of three; 965 built (including 12 for the United States Navy as R4D-1). C-47A C-47 with a 24-volt electrical system, 5,254 built including USN aircraft designated R4D-5 RC-47A C-47A equipped for photographic reconnaissance and ELINT missions SC-47A C-47A equipped for Search Air Rescue; redesignated HC-47A in 1962 VC-47A C-47A equipped for VIP transport role C-47B Powered by R-1830-90 engines with two-speed superchargers (better altitude performance) to cover the China-Burma-India routes, 3,364 built VC-47B C-47B equipped for VIP transport role XC-47C C-47 tested with Edo Model 78 floats for possible use as a seaplane C-47D C-47B with second speed (high blower) of engine supercharger disabled or removed after the war AC-47D Spooky Gunship aircraft with three side-firing .30 in (7.62 mm) Minigun machine guns EC-47D C-47D with equipment for the Electronics Calibration, of which 26 were so converted by Hayes in 1953; prior to 1962 was designated AC-47D NC-47D C-47D modified for test roles RC-47D C-47D equipped for photographic reconnaissance and ELINT missions SC-47D C-47D equipped for Search Air Rescue; redesignated HC-47D in 1962 VC-47D C-47D equipped for VIP transport role C-47E Modified cargo variant with space for 27–28 passengers or 18–24 litters C-47F YC-129 redesignated, Super DC-3 prototype for evaluation by USAF later passed to USN as XR4D-8 C-47L/M C-47H/Js equipped for the support of American Legation United States Naval Attache (ALUSNA) and Military Assistance Advisory Group (MAAG) missions EC-47N/P/Q C-47A and D aircraft modified for ELINT/ARDF mission, N and P differ in radio bands covered, while Q replaces analog equipment found on the N and P with a digital suite, redesigned antenna equipment and uprated engines C-47R One C-47M modified for high altitude work, specifically for missions in Ecuador C-53 Skytrooper Troop transport version of the C-47 that lacked the reinforced cargo floor, large cargo door, and hoist attachment of the C-47 Skytrain. It was dedicated for the troop transport role and could carry 28 passengers in fixed metal seats arranged in rows in the former cargo space; 221 built. XC-53A Skytrooper One testbed aircraft modified in March 1942 with full-span slotted flaps and hot-air leading edge de-icing. Converted to C-53 standard in 1949 and sold as surplus. C-53B Skytrooper Winterized and long-range Arctic version of the C-53 with extra fuel tanks in the fuselage and separate navigator's astrodome station for celestial navigation; eight built. C-53C Skytrooper C-53 with larger port-side access door; 17 built. C-53D Skytrooper C-53C with 24V DC electrical system and its 28 seats attached to the sides o…

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Large numbers of C-47s, C-117s and other variants survive, on display in museums or as monuments; operated as warbirds; or remaining in service.

As part of the 75th-anniversary commemoration in June 2019, 14 American C-47s and another group of 'Daks' from Europe retraced the route across the English Channel to Normandy taken by roughly 850 of these aircraft on D-Day. Among them were That's All, Brother, Betsy's Biscuit Bomber, Miss Montana, Spirit of Benovia, D-Day Doll, Boogie Baby, N47E Miss Virginia, and Whiskey 7.