WHSmith has confirmed that it will take over the empty business premises, with hopes to be up and running by the autumn.
The news follows seven months without a retailer at the site, with many residents and fellow retailers questioning when it would be occupied again.
Ian Blackaller, chairman of the Uckfield Chamber of Commerce, said: "Quite simply it's really good news for Uckfield. There have been a number of shops that have closed down due to the recession and the High Street has not looked good.
"The fact they are opening a WHSmith is going to improve the ambience of the whole place."
Spokesman for WHSmith, Sue Barratt confirmed the rumours, saying: "WHSmith is delighted. The new store will offer a range of books, stationery, newspapers and magazines."
It is not good news for all, though. Kevin Fowler, owner of Potters Book Shop on the High Street, raised concerns about the announcement.
He said: "It might very well bring people into the town, but for us it's definitely going to be negative if they are selling books."
Despite his worries, Mr Fowler said it was a "good thing" that the shop would no longer be empty, adding: "It's not nice seeing the empty shops and there were quite a few here and they are gradually filling up."
The launch of an online version of Woolworths at the beginning of July led shoppers in both Uckfield and Crowborough to question the length of time the buildings had been dormant in their shopping centres.
Mr Blackaller said: "There were rumours going round that firms like Iceland were going in there or Next, but nothing happened.
"I am surprised it took so long, but it is good news, it's good for the local public."
The chain describes itself as "one of the UK's leading retailers" with more than 500 High Street stores across the country, and a further 120 stores at airports, train stations and service stations.
Uckfield town councillor Jim Molesworth Edwards said: "I think it's wonderful. I can't see it's going to be of any detriment to the other shops.
"I think it will attract more people into the High Street having WHSmith there."
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