The USAAF was enthusiastic about the Commando, and a total of 1,479 C-46s and C-46As were built by Curtiss in plants at Buffalo (1,039 "C-46A-CU" Commandos), Saint Louis (two "C-46A-CS" Commandos), and Louisville, Kentucky (438 "C-46A-CK" Commandos). They were flown by the US Army Air Transport Command, Air Service Command, and Troop Carrier Command. About 40 C-46As were passed on to the US Marine Corps with the designation "R5C-1", and some of these aircraft were later passed on to the US Naval Air Transport Command in turn. Demand for the type was so great that the USAAF placed an order for 500 C-46A Commandos with Higgins Industries, famed for construction of landing craft and torpedo boats, but only two "C-46A-HI" Commandos were actually built by Higgins, being delivered in October 1944.
The Commando initially went into service on the South Atlantic ferry route, and would also participate as a glider tug in the Rhine crossings in March 1945. However, due to its long range, it was primarily used in the Pacific and China-Burma-India (CBI) theaters, becoming the primary cargolifter for ferrying supplies from India to China over "the Hump", the Himalaya Mountains, after the Japanese shut down the Burma Road in 1943. Commandos of Colonel Edward H. Alexander's "India-China Wing" of the USAAF Air Transport Command flew from primitive airstrips in the Indian state of Assam, climbing with overload cargoes to clear ridges from 3.7 to 4.3 kilometers (12,000 to 14,000 feet) high, to land at Chunking and drop off their loads for USAAF General Claire Chennault's 14th Air Force and Nationalist Chinese forces.
The loss rate of the C-46 was high and it had a mixed reputation with aircrews. Partly the problem was the fact that environment was very harsh, operating conditions were difficult, and Japanese fighters were an occasional threat. During one attack, Captain Wally A. Gayda shoved a Browning Automatic Rifle out one of the forward cabin windows and shot down the attacker. However, stories still circulate that the C-46 also suffered from a large number of engineering and manufacturing faults, in particular a leaky hydraulic system. Crews were said to take a barrel of hydraulic fluid along on flights to make sure that the hydraulic systems were topped off before they were used. There was also apparently a fuel leak problem that took a long time to work out, with aircraft being lost in midair explosions at a steady rate until it was. It doesn't appear that the C-46 was an inherently bad aircraft, it was just rushed into service without the level of qualification that it would have been run through in peacetime, and it took a lot of work to get the bugs fixed. The aircraft's detractors called it the "Curtiss Calamity" and the "Leaky Tiki", though it was also more affectionately named "Dumbo", after the flying baby elephant in Walt Disney's 1941 animated movie.