The village name 'Claydon' is Anglo Saxon in origin, and means 'clay hill'. The affix 'Middle' is used to differentiate the village from nearby Steeple Claydon, and East Claydon, and from the hamlet of Botolph Claydon. In the Domesday Book of 1086 the Claydon area was recorded as Claindone.
Middle Claydon is the location of Claydon House, that was the home of Sir Edmund Verney, an English Civil War Royalist hero, and of Florence Nightingale.
The parish church is dedicated to All Saints.