U-Need-Us, in Arundel Street, announced its closure in February 2019.
The shop, which was well known for its fancy dress, joke items and party goods, had been run by the Searle family for 96 years.
At the time, manager Debbie Haggan, whose grandfather set up the shop, said online competition had contributed to its decline.
The shop ceased trading in March 2019 and the building was put up for sale.
On Sunday, the family locked the shop doors for the last time, following the sale of the building.
Stephen Searle posted photos of their last day to Facebook.
He said: ‘So today after our beginnings in 1923 the Searle family’s proud presence in Portsmouth town centre officially ended.
‘The premises have new owners and the shop will take on a new life and we also believe a part change of use.
‘We wish it well as our once-lively shopping centre evolves into something different as is needed for today’s rapidly changing times.
‘It was only a building but it holds so many memories within its walls, so many smiles, so much joy and so many countless memories.
‘Thank you Portsmouth and to all of you far and wide who played a part in our proud history. We’ll be raising a glass to you all this evening.’
He said the building had been sold to a local developer, and the ground floor will continue as either retail or restaurant use, with a potential for flats on the upper floors.
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