A Roman road, from Akeman Street (the A41) to Thornborough, is though to pass through East Claydon parish. There is no other evidence for Roman activity in the parish.
East Claydon was recorded in Domesday and was part of Bernwood Forest from before this time. Bernwood had been a hunting forest from the time of Edward the Confessor. It grew to its largest extent under Henry II. The whole area was not covered by woods; in the medieval period a forest was a place where deer roamed for hunting and so included open land, villages and fields. All those who lived in the forest were not allowed to hunt or even gather wood without a special licence from the king. Bernwood Forest was finally disafforested in the reign of James I in 1635, although it had been shrinking in size since the time of King John (1199-1216).
East Claydon parish was more densely settled in the medieval period. A medieval moat with surrounding house platforms is known from aerial photographs north of Whitehouse Farm and may be the site of a deserted medieval village. Another complex of moat and house platforms is known north-west of the church. West of the modern village, there are also medieval village earthworks, including a pond, around Verney Farm. North of Botolph Farm there are also medieval house platforms of Botolph Claydon. Botolph Claydon probably got its name from the Botyl Well, a name that was later corrupted into St Botolph’s well. There are several medieval house platforms around the site of the well, as well. It was also probably the site of the parish windmill, which is mentioned in the 14th and 16th centuries.
The Salden estate map of 1599 marks the field at the boundary of Winslow and Granborough as Mill Hook, suggesting the site of a watermill. St Mary’s church has a 14th century chancel and 15th or 16th century tower and is the oldest surviving building in the parish. One of the oldest surviving secular buildings in East Claydon is Whitehouse Farm, which may date back to the 16th century. It is thought to have been one of the manor houses of the Lee family, who also had places in Quarrendon and Ditchley in Oxfordshire. The site of a former manor house is mentioned in 1310, but it may not have been on the same site. Slightly older than Whitehouse Farm are 5 Orchard Way and Pond Cottage, which are 15th century cruck-built houses. Other listed buildings in the parish date to the 17th century, such as 45 Botyl Road, or the 18th, like Botolph House.
In the 19th century the Aylesbury to Buckingham railway was built and passed through East Claydon. It opened in 1868 and was run by the Great Western Railway but was later taken over by the Metropolitan line and then London Transport. It closed in 1936. There was a station on Granborough Road but it was also closed in 1936 and the buildings were demolished, similarly the Winslow Road station.