Other innovations included auxiliary power units, power-boosted flight controls, alternating current electrical system and air conditioning.

The four 1,450 hp (1,080 kW) Pratt & Whitney R-2180-A Twin Hornet 14-cylinder radials were all mounted with noticeable toe-out, particularly the outer pair.

[6] The prototype (NX18100, s/n 1601) first flew, without incident, on June 7, 1938 from Clover Field in Santa Monica, California, piloted by Carl Cover.

Although the aircraft was relatively trouble-free, the complex systems proved to be expensive to maintain and performance was below expectations, especially with an increase in seating to 52 and gross weight to 65,000 lb (29,484 kg).

In late 1939, the DC-4E was sold to Imperial Japanese Airways, which was buying American aircraft for evaluation and technology transfer during this period.