The Spring Gardens premises have been empty since April 2019, when the shop closed after serving the town for 85 years.
But work is now underway to bring the site back into use, with one company signing a 10-year lease to the site, as four businesses look to open there.
Simpson Furniture, which has been holding a pop-up shop in the shopping centre for several months, is taking over a portion of the store. Work has already started to create a glass-fronted entrance for the business.
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Eugene Stack, director of operations for the furniture company, said: “We have signed a 10-year lease to be in the building which is a big commitment to the town.”
The company has only been operating for four years with the Buxton showroom set to be their third, and their biggest.
Eugene said: “We will be taking over 5,000 sq ft so this is a big jump for us but we believe in the town.
“We started with the pop-up shop in The Springs but its nature is transient and we wanted a more secure home and the former M&S building is perfect.”
Simpson Furniture sells sofas, beds, dining room furniture and mobility chairs as well as accessories and gifts.
The store, which is planned to be open in a few months, is just one of the new companies to lease part of the building.
In December, plans were submitted to High Peak Borough Council to open a new hotel in the building with a cafe and restaurant on the ground floor. The council has deemed the application invalid.
The Buxton Advertiser has contacted the applicant to get more information about these proposals and is awaiting a response.
Eugene said he is not sure what the fourth business on the site will be but says he does know there will be four.
The pedestrian walkway between Spring Gardens and The Springs Shopping Centre is still going to be in place although the details of this have not been finalised yet, he added.
Eugene said: “Buxton is going to thrive in the coming years. The opening of The Crescent and the Future High Streets Fund are all putting money into the town which people will see the benefit of in the coming years.
“Buxton is a destination area where people will travel to for a day out. The catchment area is huge covering Sheffield, Chesterfield, Derby and Manchester so it is the right time for us to be moving into a more permanent home in the town.”
High Peak MP Robert Largan said he was pleased the building was being put back into use.
He said: “It is such a prominent building in the town centre and one which needs to be occupied.
“It is a huge retail space which has been shut for a while so anything which sees empty buildings have another life and bring people into the town can only be a good thing.”