The Oxford (nicknamed the 'Ox-box') was used to prepare complete aircrews for RAF`s Bomber Command and as such could simultaneously train pilots, navigators, bomb aimers, gunners, or radio operators on the same flight. In addition to training duties, Oxfords were used in communications and anti-submarine roles and as ambulances in the Middle East.

The Oxford was the preferred trainer for the Empire Air Training Scheme (EATS) andBritish Commonweahlt Air Training Plan (BCATP) which sent thousands of potential aircrew to Canada for training. 27 Oxfords were on the strength of No 4 Flying Training School RAF Habbaniya, Iraq in early 1941 and some were converted locally for use as Light Bombers to help in the successful defence of the School against threatening and attacking Iraqi forces.

In 1941, the aviatrix Amy Johnson went missing in an Airspeed Oxford, presumably crashing into the Thames Estuary.

After the war, 152 surplus Oxfords were converted into small 6-seat commercial airliners called the AS.65 Consul. A few Oxfords were acquired by the Hellenic Air Force and used during the Greek Civil War by No. 355 Squadron RHAF.

Although the Oxford was equipped with fixed-pitch Fairey-Reed propellers , the cockpit contained a propeller pitch lever which had to be moved from "Coarse" to "Fine" for landing. This was done to reinforce this important step for training pilots. The Oxford had a tendency to yaw due to the "handing" or rotation of the engines, inducing p-factor. This condition was nearly impossible to correct by trimming the aircraft and landings could be tricky with a tendency for the aircraft to ground loops.

Oxfords continued to serve the Royal Air Force as trainers and light transports until the last was withdrawn from service in 1956. Some were sold for use by overseas air arms, including the Royal Belgian Air Force.

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Airspeed Oxford Mk.I, P6823/24, No.14 SFTS, Cranfield, RAF, 1940.
Airspeed Oxford Mk.I, L4580/15, No.3 FTS, South Cerney, 1938.
Aispeed Oxford Mk.II, T1244/H5, No.6 SFTS, Little Rissington, Gloucestershire, Great Britain, Februari 1943. From April to November 1944 this machine served with USAAF at Bovindon and Alconbury air bases.