The growth of operations on Boeing Air Transport's San Francisco-Chicago route resulted in the design and development of a purpose-designed passenger transport, the Boeing Model 80, first flown during August 1928. A large unequal-span biplane, with the lower wing of reduced chord, the Model 80 had a wing structure of wood, fabric-covered, and a fuselage and tail unit of welded steel tube, also fabric-covered. Landing gear was of fixed tailwheel type, and power was provided by three 306kW Pratt & Whitney Wasp radial engines. These were mounted in the classic tri-motor configuration, one in the fuselage nose, and one each side of the fuselage, between the biplane wings.

The main cabin of the Model 80 accommodated 12 passengers, plus a flight stewardess. This was very much an innovation, for although some European airlines had introduced male stewards at an earlier date, Boeing stewardesses, all registered nurses, represented the first of the air hostesses that are now an integral part of civil airline operations. Another feature of the Model 80 was the provision of a separate enclosed flight deck for the pilot and co-pilot/navigator, a development that was not accepted enthusiastically by all flight crew. Four of these aircraft were built, entering service with Boeing Air Transport in the late summer of 1928.

The Model 80s were followed by 10 of the much improved Model 80A, this type having more powerful Pratt & Whitney Hornet engines, refinements to the-wing, improved streamlining and, because of the increased power available, a cabin layout to accommodate a maximum of 18 passengers.