On Friday a fire believed to have started at an art gallery in Exeter city centre soon raged to the nearby Royal Clarence Hotel.
About 110 firefighters, police and paramedics were called to the blaze which began shortly after 5am. Devon and Cornwall Police said road closures were in place around the city centre. No injuries have been reported but the building has suffered severe damage.
Dr Todd Gray, a historian at the University of Exeter, said: "The Royal Clarence is in the heart of what was not just the Medieval city but within the precincts of Roman Exeter. For 2,000 years this area has been the focus of the city's religious and commercial life."
He added: "What is so particularly heart-breaking about this loss is that these buildings escaped the Blitz of 1942 when so much of Exeter was destroyed. We have so little left and hopefully the fire will be contained and not spread further."
The Royal Clarence Hotel has stood on the same spot for 300 years and is reported to be the oldest hotel in England. The 18th century coaching inn, which is now called the Abode Hotel, is part of the Andrew Brownsword group.