Initially engaged in anti-submarine warfare in the Aegean, it was sent to Russia in December 1918 to support White forces against the Bolsheviks.

The unit was based at Petrovsk from January to 1 September 1919, when it was disbanded.

221 Squadron was reformed as part of Coastal Command.

It flew Vickers Wellingtons on reconnaissance and anti-submarine patrols in the Atlantic, first out of England, then Northern Ireland and later Iceland.

The squadron relocated to the Middle East in January 1942 and operated in the Mediterranean for the rest of the war, disbanding at Idku, Egypt on 21 August 1945.