An estimated £2.2m worth of furniture, paintings, jewellery and silver, many untouched for decades, will be sold across two auctions in Geneva and London.
Bamber Gascoigne, broadcaster and nephew of the Duchess, inherited the red-brick 16th century mansion and the 400-acre estate when she died in 2014, much to his surprise. He will use funds raised from the sale to undertake essential restoration work on the manor to ensure that it continues "to stand as a monument of its remarkable past".
West Horsley Place dates back to the 11th century. The house has received an array of notable guests, including Henry VIII and, legend has it, the embalmed head of Sir Walter Raleigh.
It was also used as the depository for the famed papers of Sir Edward Nicholas, secretary of state to Charles I, now largely in the British Museum.
Choice pieces of jewellery will be offered in Geneva on May 12 with the dispersal of the main collection taking place in London on May 27-28.