A 5,000 mi (8,000 km) flight took 33 hours at its 152 mph (245 km/h) cruising speed; the crew was made up of several shifts, and bunks allowed them to sleep when off duty.

The specification that produced the XB-15 began in mid-1933 as "Project A", USAAC discussions regarding the possibility of flying a very large bomber with a range of 5,000 mi (8,000 km).

[2] In April 1934, the USAAC contracted with Boeing and Martin to design a bomber capable of carrying 2,000 lb (910 kg) at 200 mph (320 km/h) over a distance of 5,000 miles.

[8] However, Boeing engineers projected that the prototype would be capable of carrying the heaviest air cargo to date: a load of 8,000 lb (3,600 kg).

In 1938, the USAAC proposed to update the XB-15 to make the slightly larger Y1B-20, again using four Wright Twin Cyclones as with the Boeing 314, but the Secretary of War, Harry Hines Woodring, canceled the project before construction began, in favor of the expensive Douglas XB-19.

Boeing went ahead with an internal redesign of the XB-15 called Model 316, a very heavy bomber with a high wing, a pressurized cabin and tricycle gear.

The progression of design work starting with the XB-15 finally bore fruit with the Model 345 presented to the USAAC in May 1940, the very heavy bomber which resulted in the USAAF's Boeing B-29 Superfortress.

Commanded by Major Caleb V. Haynes, the aircraft carried 3,250 lb (1,470 kg) of American Red Cross emergency supplies to Santiago, making only two stops along the way, at France Field in the Panama Canal Zone, and at Lima, Peru.

[9] Haynes piloted the XB-15 again on 10 June 1939 to return home the body of Mexican flier Francisco Sarabia who had died in a crash in the Potomac River.

After flying back from Mexico City, Haynes and his copilot William D. Old undertook flight tests at Wright Field with heavy loads.

[11] Haynes was awarded certificates issued by the National Aeronautics Association (NAA) for an international record for "the greatest payload carried to an altitude of 2,000 meters".

[12] Flying from Langley, the XB-15 arrived at Albrook Field in Panama on 10 April 1940 and immediately began classified bombing tests of canal lock protections, commanded by Haynes and including Captain Curtis LeMay as navigator and Lieutenant John B. Montgomery as bombardier.

[13] During World War II, the XC-105 carried freight and personnel to and from Florida, and throughout the Caribbean, based out of Albrook Field beginning in June 1943.

Hundreds of young women were flown in "Grandpappy" from Miami to the Canal Zone to engage in US government work; these trips were dubbed the "Georgia Peach Run".