Blenheim Palace is putting the "majority of its staff" on furloughed leave due to the coronavirus outbreak.
Chief executive Dominic Hare said the impact of the pandemic on the estate was "far bigger than the credit crunch and foot and mouth combined".
The world heritage site in Woodstock, Oxfordshire, said 78% of its workforce would be placed on leave from 1 April.
The palace's website says the estate employs more than 450 people in permanent and seasonal roles.
Most of its facilities, including the palace, formal gardens and pleasure gardens, were closed on Sunday in response to new government guidelines.
Blenheim Park remains open to a limited number of visitors to allow social distancing rules to be observed.
Mr Hare said the estate, which is home to the 12th Duke of Marlborough and his family, was "incredibly resilient" and a small team would remain working to maintain the site on reduced salaries.
He said the government's job retention scheme gave the charity a "very sensible pathway to protect as many jobs as possible".
"Events of this magnitude strike at the heart of even the strongest of organisations," he added.
"We can say with certainty that the world which follows this crisis will be different to the world today and we have every confidence that Blenheim, the most successful and adaptable of all institutions, will emerge as strong as ever."
The house, which stands in 2,000 acres of parkland, has 187 rooms - more than Buckingham Palace and Windsor Castle - and was the birthplace of Sir Winston Churchill in 1874.
It opened to the general public in 1950, and has also raised money by being a popular site for film-makers, featuring in franchises including James Bond, Mission: Impossible, and Transformers.