The Douglas Transport was originally developed for TWA. It entered production in 1933 as the more powerful 529kW Wright SGR-1820-F3 Cyclone-engined and lengthened (14-seat) DC-2. The first of 20 ordered by TWA flew on 11 May 1934 and deliveries started soon after. The early DC-2 were so successful that by June 1934 orders for 75 aircraft had been received from airlines in both the US and abroad. Subsequent orders were received from American Air Lines, Eastern Airlines, Pan American Airways and from numerous foreign operators - the first exported DC-2 being flown by KLM in the autumn of 1934.

By September 1935 110 had been ordered and to meet the demand Douglas was producing one aircraft every three days. Such was the importance of the DC-2 that in 1934 Anthony Fokker acquired exclusive European rights to sell the Douglas Transport in Europe. In addition to commercial aircraft, DC-2 were purchased by the US Navy and USAAC and others were impressed into military service during World War II to serve with the Allied forces.