It follows an extensive four-year restoration project after the Bank Buildings branch was destroyed by an accidental fire in August 2018.
The retail giant said it was targeting the first week of November for the reopening.
The redevelopment work has included demolishing and rebuilding the site in a huge project in the retail heart of the city.
The new store will feature 88,200 square feet of retail space, a Disney cafe on the second floor and a new nail and beauty studio.
Primark’s existing store in Castle Street will merge with the restored Bank Buildings site to create the larger store.
The smaller store at Fountain House, Donegall Place, will close in the days before the Bank Buildings reopening, with all employees transferring to the new store.
We have put our heart and soul into retaining, conserving and restoring this much-loved historical building
Paul Marchant, Primark chief executive, said: “We want to thank the people of Belfast for their ongoing support and patience whilst we undertook the extensive rebuilding works at our iconic Bank Buildings site.
“We recognise how much the business community and wider city of Belfast has been affected by the devastating fire at our store back in 2018.
“We have put our heart and soul into retaining, conserving and restoring this much-loved historical building.
“We are nearly there with this redevelopment, and we cannot wait to finally reopen the doors and welcome our customers and our colleagues back into our Bank Buildings store.”
Lord Mayor of Belfast Tina Black said: “This is a major investment in Belfast city centre after a challenging time for our local economy.
“The devastating fire at Bank Buildings in 2018 was a turning point for our city; it acted as a springboard in bringing elected members and city partners together to examine and trial new ideas and concepts to support recovery and regeneration and increase what the city centre has to offer.
“Many of these projects have now been incorporated into our Future City Centre programme.
“This has been a long and complex restoration project, and local traders and shoppers have shown great patience and resilience.
“We hope the opening of Primark’s extended flagship store will provide a major boost to businesses, particularly in the run-up to the busy Christmas season.”
Belfast Chamber chief executive Simon Hamilton said: “This is really positive news for Belfast and will provide our city centre with a much-needed boost.
“Primark is an exceptionally popular store that drives footfall into Belfast from far and wide and its loss after the fire nearly four years ago was acutely felt across the city centre.
“It is a massive vote of confidence in Belfast that Primark is investing so much and coming back bigger and better, and I am sure it will greatly assist Belfast in its ongoing recovery and regeneration.
“Reopening the store at Bank Buildings will also, in effect, reopen parts of the city centre that have been closed off or difficult to access due to the construction work at Primark, and this too will hugely help our city centre.”
Retail NI chief executive Glyn Roberts said: “Without a doubt this reopening will be a much-needed boost for the city centre and its traders. This store was always a huge footfall driver for our members in Royal Avenue and the city centre as a whole.
“Whilst the city centre is experiencing serious challenges at present, its future has huge potential to be a fun, family friendly destination with a dynamic retail and hospitality offering.”