It has been suggested that the name Molesey means 'a flat, marshy island' and that the River Mole, which flows through the area, is a back naming from 'Molesey River'. The river was originally known as the 'Emlyn Stream'. Near here a branch of the Mole, the River Ember, leaves the main river and enters the Thames opposite Hampton Court Palace. The Mole itself once flowed into the Thames further upstream at a point where the present Hampton Court Bridge now crosses the Thames.

During the early 1930s, when the Hampton Court Way and Bridge were built, the Mole was redirected to flow into Ember and both rivers now enter the Thames in a single widened and straightened channel once occupied only by the Ember. There have been further alterations to the courses of these two rivers in a major flood prevention scheme since serious flooding in the area in 1947 and 1968.

The present Hampton Court Bridge across the Thames here was designed by the famous architect, Sir Edwin Lutyens, as was the bridge which crosses the Mole/Ember a few hundred yards south. The first bridge across to Hampton Court was built of wood in 1750, rebuilt in 1778 and rebuilt again, this time in iron, in 1865. The alignment of Bridge Street in East Molesey shows clearly that these bridges crossed the river from a position upstream of the existing bridge. In earlier times the river was fordable and later there was ferry crossing here. This was an important crossing from the early 16th century because of the position of Cardinal Wolsey's, later Henry VIII's, Hampton Court Palace opposite on the Middlesex bank. There is a weir and a lock on the Thames at East Molesey.

East Molesey was divided into two manors at the time of the Domesday Survey in 1086 but the overlord of both was Richard de Tonbridge. John D'Abernon held one of the manors from Richard. In the days of King Edward the Confessor (1042-1066) it had been held by Aelfric. During the second quarter of the 12th century this manor passed to Merton Priory and became known as Molesey Prior. In 1536 John, Prior of Merton, conveyed the manor to Henry VIII. The manor then passed through a number of hands until it was purchased by Baron Hotham in the late 18th century. It remained with the Hotham family until the 20th century.

The second manor at East Molesey was also in the overlordship of Richard de Tonbridge but in 1086 it was held by Roger D'Abernon. It had been held by a certain 'Toki' in Edward the Confessor's reign. It is likely that this manor also formed part of the estate that was granted to Merton Priory in the 12th century and which subsequently became known as Molesey Prior.

The present parish church of St Mary is a Victorian replacement for a small medieval church and a second church at Kent Town, East Molesey, is also Victorian.

The railway opened in 1849 but the terminus station here was named 'Hampton Court' despite the fact that it is in East Molesey. Since then East Molesey has been extensively developed as a popular riverside residential area.