Drayton was the home of the Saxon Kings of Wessex. The early monarchs seem to have lived in North Berkshire and only later moved down to Winchester. They were almost certainly members of the Gewissae tribe, the 'trusted ones' whom the Romans had invited over to help defend Britannia. They settled not far away in the Roman town at Dorchester-on-Thames (Oxfordshire). Their kings may have later moved out to Long Wittenham but, by the 7th century, they had established a major palace complex on the edge of Drayton, on the site of a previous village which spread over the border into Sutton Courtenay. Aerial photography and small-scale excavation have revealed a group of five vast Saxon halls (a sixth was further east). The main feasting hall was 82ft long by 26ft wide, making it bigger than the great hall excavated at Yeavering (Northumberland) where King Edwin of Northumberia lived. The others were smaller and may have been the king's bower (largely for the ladies) and guest accommodation. Finds of fine jewelry and goldwork have been made by metal detectorists, including an eagle mount and a jewel encrusted sword toggle like those found in the Royal East Anglian burial mounds at Sutton Hoo (Suffolk).

Today, Drayton is an attractive village with ancient cottages, some dating back to the late 14th century. It lost many others in the 'Great Fire of 1780' after which much of the village was rebuilt by public subscription. The village cross, on an ancient base, stands at the major road junction, but the centre of the old settlement is along the 'High Street' near the parish church. This building is famous for its beautifully carved 15th century altarpiece. Despite the church dating back to 1200, the area was a dependency of St. Helen's in Abingdon until 1867. Traditionally, the villagers have almost all worked on the land. However, the enclosure of their common land seems to have come early to Drayton for it was causing unemployment as early as 1517.

Drayton Manor stands south of the High Street. Its western part dates from the 15th century and a fireplace and parts of the screens passage from when it was a medieval hall house survive. Unfortunately, it only has an early 20th century neo-Georgian facade. There is also a large three-bay addition of about 1700 with a very posh Corinthian-style doorway. It was probably added by the Southcotts, a recusant Catholic family who passed the estate around the family to avoid having it confiscated. They helped build the famous market cross in Abingdon. Previously, before the Dissolution of the Monasteries, the manor-house had been a grange of Abingdon Abbey.

During the Civil War, when Prince Rupert mounted a major attack on the parliamentary garrison at Abingdon, in January 1645, eighty Royalist soldiers from Faringdon fought with the Roundhead horse at Drayton and Sutton Wick. They were quickly sent packing.