In 1930, Boeing created the revolutionary Monomail, which made traditional biplane construction a design of the past. The Monomail wing was set lower, was smooth, was made entirely of metal and had no struts (cantilevered construction). The retractable landing gear, the streamlined fuselage and the engine covered by an antidrag cowling added up to an advanced, extremely aerodynamic design.

The Monomail Model 200 was a mail plane, and the Model 221 was a six-passenger transport. Both were later revised for transcontinental passenger service as Model 221As.

The major drawback of the Monomail was that its design was too advanced for the engines and propellers of the time. The airplane required a low-pitch propeller for takeoff and climb and a high-pitch propeller to cruise. By the time the variable-pitch propeller and more powerful engines were available, the Monomail was being replaced by newer, multiengine planes it had inspired.