The inferno at the National Trust’s Clandon House is believed to have started in the basement before ripping through the building and spreading to the roof.
Around 80 firefighters worked into the night to bring the flames under control at the estate near Guildford in Surrey.
Staff and volunteers were safely evacuated when the blaze broke out just after 4pm today.
At least one wing of the Grade I listed building appears to have been gutted and the roof has caved in.
Many of the irreplaceable items were damaged or destroyed, with a salvage operation under way to try and save as much as possible.
National Trust director Helen Ghosh said: “The most important thing for me is that no one has been hurt in this awful fire and that everyone is safe.
“But it has been heartbreaking to witness the terrible damage to this wonderful mansion, which means so much, to so many people.
“This will come as a terrible shock and a devastating personal blow to all our devoted staff and volunteers.
“We’ll continue to work closely with the fire brigade, who are working hard to bring the blaze under control. We’d like to thank them again for their efforts.”
Thick black smoke could be seen pouring from the building and nearby resident Phoebe Grant said flames were “shooting out of the building”.
The 18-year-old told Trinity Mirror: “They’ve evacuated the whole area, they won’t let anyone near Clandon Park.
“There’s still smoke and flames coming from the roof. It looks like part of the roof has caved in.”
Another local resident, John Covey, told Get Surrey that fire crews were struggling to control the blaze.
“The trouble is a lack of water,” he said.
“They can’t get enough pressure up there.
“They had it under control but then the water went down and the flames went up again. It’s a disaster.”
Others reportedly heard loud bangs coming from inside.
Clandon Park was built in the 1720s and contains a large collection of 18th century furniture, porcelain and textiles.
It has been managed by the National Trust since 1856 and is a popular venue for weddings.
One woman, named on her Twitter account as Hannah, said: “Poor ClandonPark hope it’s not too badly damaged. Had the best wedding there last year. It’s the most beautiful venue”
Some 16 crews were deployed to the scene along with three aerial ladders and three water carriers.
A spokesman for Surrey Fire and Rescue Service said the cause of the blaze will be investigated.
“It was a significant fire throughout the building and it is believed to have started in the basement,” he said.
“It spread and has spread to the roof.
“The full extent of the damage is not known but work is ongoing to salvage what can be salvaged from inside.
“Everyone was evacuated safely so fortunately there are no casualties.”