The DC-5 prototype and four production DC-5s were built before World War II. The 16-seat airliner featured innovative tricycle landing gear and was intended for shorter routes, but by the time it entered service in 1940, the war was under way.

Only five civilian DC-5s were built as the Douglas Aircraft Co. turned its attention to military airplanes. William Boeing bought the prototype for his personal use. It later served with the U.S. Navy as the R3D-3. KLM bought the other four airplanes and these were used to evacuate civilians from Java to Australia in 1942. One was captured by the Japanese, one was scrapped after a landing accident, and two later joined the U.S. Army Air Forces (USAAF) as C-110s.