The 4th Duke of Devonshire was a prominent Whig politician, and served as Lord Lieutenant of Ireland and, briefly, as Prime Minister of England (November 1756-May 1757).

In 1748 the Duke married Lady Charlotte Boyle (1731-1754), the only surviving daughter and heiress of the architect and connoisseur 3rd Earl of Burlington and Lady Dorothy Savile.

This marriage brought new estates to the Cavendish family, including Lismore Castle in County Waterford in Ireland, Londesborough Hall and Bolton Abbey in Yorkshire, and Burlington House and Chiswick House in London. The inheritance included all of Lord Burlington's architectural books and drawings as well as many paintings and the entire contents of his houses.

At Chatsworth, the 4th Duke made great changes to the park and garden. Having decided that the house should be approached from the west, he pulled down the old stables and offices which interrupted the view on this side and razed the cottages of Edensor village which were visible from the house.

The architect James Paine (c.1716-1789) was commissioned to build new stables, and he also designed a new bridge upstream of the house. Land to the west of the river, including what remained of Edensor village, was enclosed to become the park as it is today.

Lancelot (Capability) Brown (1716-1783) was commissioned to replace the 1st Duke's formal garden and park with the natural, romantic look which he had helped bring into fashion.

The 4th Duke died in 1764 and was succeeded by his eldest son, William.

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