There is archaeological evidence the site was used in Roman times for brick and tile making.
In mediaeval times the site was a part of the endowment of the Priory of St Bartholomew's which operated St Bartholomew's Hospital in London. This gave it the name Cannons, canon was an archaic term for certain orders of monks including the Augustinians of St Bartholomew's Priory. At the dissolution of the monasteries the land was sold into private hands in 1543. A large house was built during the 16th and 17th centuries at one point owned by Thomas Lake, James I's Chancellor of the Exchequer.
James Brydges was an MP for Hereford who achieved the post of Paymaster General to the Forces. He retired in 1713 with a fortune of £600,000, worth £58,000,000 today, he had gained by speculation with the money in his care. Brydges had inherited Cannons from his first wife Mary who died in 1712. In 1713 he married his cousin Cassandra Willoughby and began to enlarge the house. Brydges took personal control of the project and it was the work of a string of architects and landscape gardeners, who changed as they fell into and out of favour. He used the house as a setting for his patronage of the arts stocking it with paintings, sculpture and holding opera performances. It was completed by 1720.
Brydges was made earl of Caernavon in 1714 and later became duke of Chandos. His fortunes were damaged by financial losses in the South Sea Bubble of 1720. However, when his wife died in 1735, he remarried a wealthy 43 year-old widow, Lady Lydia Davall, who had £40,000 to her name.
Chandos died in 1744 and his debts were by then so great that his heirs had no choice but to sell the house and contents in a demolition auction of 1747. The architectural building adornments were sold off to other grand projects. The Palladian columns form the portico of the National Gallery in London.
A more modest house was built on the site in 1760 by William Hallett who had acquired wealth through his skill at cabinet making. This was itself enlarged by a succession of owners, notably Dennis O’Kelly owner of the outstanding racehorse Eclipse. By 1896 the parkland had begun to be sold off as building plots. Sir Arthur du Cros of Dunlop Rubber became tenant in 1902 and bought it in 1911. He engaged the celebrated Arts and Crafts architect Charles Mallows to remodel and enlarge the building between 1905-1908. The exterior of the current building is largely his work.
In 1929 the house was bought by the North London Collegiate School who still occupy it today. Part of the gardens remain as Canons Park in the care of the London Borough of Harrow.
The house gives its name to the modern local district, Canon's Park , which is largely built upon its parkland and is a wealthy north London suburb. This in turn gave its name to the Underground station of Canons Park on the Jubilee line.