Exeter's branch of House of Fraser to close, signs in its windows say.
The High Street store signs advertise a closing down sale ahead of it shutting in January 2019.
It is understood staff were told on Friday but managers refused to comment on such reports last week.
The chain's Plymouth branch had been earmarked for closure when it went into administration. It was saved after the company was then bought by Sports Direct.
BBC South West Business Correspondent Neil Gallacher said the news "will shock some in Exeter".
He said: "At the start of the summer it was reported the Exeter store would not close, while the larger Plymouth store would. This stance seemed to reflect Exeter's wealthier retail catchment.
"Then Mike Ashley of Sports Direct took over.
"The landlords in Plymouth - the city council and British Land - agreed a 12-month rent deal to keep the Plymouth store open.
"Curiously, in Exeter, House of Fraser owns most of its building, so whatever the pressures, it is not a simple case of the rent being too high."
Exeter's store was once the pinnacle of retail in the city.
When Exeter's Princesshay shopping complex opened 11 years ago, House of Fraser was given a makeover to try to keep it competitive.
Previously known as Colsons in the 1800s, the store has remained in the same location in High Street despite several rebuildings and rebrandings, including Devon department store brand Dingles.
It was also the first store in the city to have an escalator.
Sports Direct has been contacted for a comment.