By the middle of 1938, the type was being utilised by Air France on European routes. The first service of the type (between Paris and London) was flown on 27 March 1938 with a scheduled time of 1 hour 15 minutes. During World War II, most MB.220s were taken over as military transports, including service with German, Free French and Vichy French air forces. Air France continued to fly the aircraft (as MB.221s) after the war on short-range European routes. It sold four aircraft in 1949 but within a year all had been withdrawn from service.