Syon House derives its name from Syon Abbey, a medieval monastery of the Bridgettine Order, founded in 1415 on a nearby site by King Henry V.

The abbey moved to the site now occupied by Syon House in 1431. It was one of the wealthiest nunneries in the country and a local legend recites that the monks of Sheen had a tunnel running to the nunnery at Syon.

The abbey was closed in 1539 by royal agents during the Dissolution of the Monasteries and the monastic community was expelled.

On the dissolution of the abbey, Syon became the property of the Crown for a short time before long lease to the 1st Duke of Somerset, who had the site rebuilt as Syon House in the Italian Renaissance style before his death in 1552.

In 1541 Henry VIII's fifth wife Catherine Howard endured her long imprisonment at Syon.

In February 1542, the King's men took her to the Tower of London and executed her on charges of adultery.

Five years later, when King Henry VIII died, his coffin, surmounted by a jewelled effigy, rested at Syon House for one night before the procession continued to his burial place in St George's Chapel in Windsor.

Lady Jane Grey was living in the house in July 1553 with her husband when she received news that she was to become Queen.

In 1557 it was proposed to convert the new building to the earlier Catholic use but Elizabeth I of England acceded to the throne before this change came about.

Syon was acquired in 1594 by Henry Percy, 9th Earl of Northumberland (1564–1632) and has since remained in his family.

In the late 17th century, Syon was in the possession of Charles Seymour, 6th Duke of Somerset, through his wife, Elizabeth Seymour (née Percy).

After the future Queen Anne had a disagreement with her sister, Mary II (wife of William III, also known as William of Orange), over her friendship with Sarah Churchill, Countess of Marlborough, Queen Mary evicted Princess Anne from her court residence at Whitehall and Hampton Court.

Princess Anne came to live at Syon with her close friends, the Somersets, in 1692. Anne gave birth to a stillborn child there. Shortly after the birth, Queen Mary came to visit her, again demanding that Anne dismiss the Countess of Marlborough and stormed out again when Anne refused.

In the 18th century, Hugh Percy, 1st Duke of Northumberland, commissioned architect and interior designer Robert Adam and landscape designer Lancelot "Capability" Brown to redesign the house and estate.

Work began on the interior reconstruction project in 1762. Five large rooms on the west, south and east sides of the house, were completed before work ceased in 1769.

A central rotunda, which Adam had intended for the interior courtyard space, was not implemented, due to cost.

In 1951, Syon House was opened to the public for the first time under the 10th Duke and Duchess.

Later, in 1995 under the 12th Duke, the family rooms also became open to the public.

Most recently the Duchess added a new central courtyard with the design of Marchioness of Salisbury.

A £600K restoration was undertaken in late 2007, primarily involving work to the roof area.

In 2008 restoration work commenced on the Great Hall and a current long-term project is to restore the Adam Rooms.

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