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An Augustinian priory was founded here in 1201. The canons welcomed pilgrims en route to Winchester, who came to worship Mottisfont's relic, said to be the finger of St John the Baptist. During the Henry VIII’s Dissolution of the Monasteries, the priory was dissolved and given by the King to Sir William Sandys who turned it into a country home. Rather than completely demolishing the priory, Sandys chose to convert the church nave into the main body of his new mansion. Sections of the original mediæval church may still be seen, with the later additions built around them. The Thirteenth century cellarium also remains present today.

In the 18th century, the old monastic cloisters and Tudor courtyard were demolished creating the modern appearance of the estate's facade. It was at this time that the owners changed the name of the house to "Mottisfont Abbey". It has been speculated that the word "Abbey" was added to the name "Mottisfont " as that the name was considered more romantic than the historically-correct "Priory" (Archive Link national Trust archived link).

The house and grounds were gifted to the National Trust in 1957 and are open to the public. The house is a Grade I listed building (List entry Number: 1093730 Link Historic England).