The USAAC announced a competition in 1934 for a new multi-engined bomber with the requirement that it carry ~2000 lbs of bombs 2000+ miles at 200+ mph (with 250 mph preferred). The three entrants to the competition were famously the Douglas B-18, the Martin 186, and the Boeing Model 299, which would go on to become the B-17. The core difference in design taken by Boeing relative to the other two competitors came in the choice of the number of engines and thus the possible size of the aircraft that could be designed. Boeing decided to use 4 engines, allowing them to design a much larger aircraft that had higher range and bombload than the competing designs. Why did Douglas and Martin choose not to design 4-engined bombers for this competition?
Douglas, after their enormously successful DC-3, also had a 4 engine DC-4E airliner on the drawing board.
As it turned out, even though the Martin and Douglas designs were light years ahead of designs from the previous decade and as fast as contemporary fighters of the early 1930s, the decision to adopt the larger 4 engine Boeing aircraft as "heavy bombers" paid off in better defensive capability, larger payload, and longer range.
The two engine designs lived on as "medium bombers" better suited for shorter range tactical support missions.