In June 1921 RAF D.H.10s opened an air-mail route across the desert between Cairo and Baghdad, but the RAF was seeking a replacement for this type and placed an order for the Avro 561, later named Andover. This was a large aircraft to be powered by a single engine, with an empty weight about 25 per cent higher than that of the twin-engined D.H.10. When Imperial Airways took over the route, the RAF requirement disappeared, and the military order was cut to just three aircraft, which served at RAF Halton in the ambulance role.

Using the wings, landing gear and tail unit of the Avro 549 Aldershot, the Andover had a new fuselage to accommodate 12 passengers, or six stretcher cases. The pilot, as was usual at that period, was in an open cockpit; the navigator, who was alongside, had access to the cabin.

The Air Ministry ordered a fourth Andover, the Avro 563, in 1925. This was configured as a 12 passenger airliner. Some cross-Channel proving flights were undertaken when the 563 was loaned to Imperial Air ways and operated under civil markings, but it subsequently reverted to its service serial number, and joined the other three Andovers.