Old newspaper offices and printing works will be transformed into loft-style housing under an £18.5 million scheme.
City Loft Developments has been given permission by Brighton and Hove City Council for the ambitious project.
It involves conversion of The Argus building, in North Road, which was the paper's headquarters before it moved to Hollingbury.
City Loft has won awards for other developments in Newcastle and Reading.
Its scheme for Brighton includes apartments designed by Conran and Partners, Sir Terence Conran's architectural practice.
Brighton estate agents Austin Gray said the scheme would start a major shake up in the local property market because of its design.
City Loft Developments, a former winner of the Sunday Times/What House? awards, specialises in converting redundant city warehouses and factories into homes, as well as creating new-build developments.
The ornate exterior of Argus House - to be re-named Argus Lofts - will be conserved by the architects while the interior will be converted into light, airy and spacious loft-style homes.
Work will start shortly and the apartments will go on sale next month, with prices starting from around £130,000.
Austin Gray is expecting high demand as City Loft schemes in Newcastle, Manchester and Reading led to queues and even would-be buyers camping outside days beforehand when the developments were released for sale.
Sales and marketing head Andre Mansoori-Dara said: "As Britain's newest city the prominence of Brighton is definitely on the increase.
"We have acquired a fantastic location in the heart of an up and coming area.
"Argus House will set the standard for conservation and regeneration for Brighton city centre and raise the benchmark for quality apartment design in the resort to a new level.
"We are working closely with the design team at Conran and Partners to create beautiful and well-crafted homes that are stylish, yet practical and affordable."
Stewart Gray, director of Austin Gray, said: "This development will have a great impact on the Brighton property market. This is the first true loft living building scheme in the centre of the city.
"Argus House stands on an island site next to Kensington Gardens and within walking distance of the main shopping centre, restaurants and nightlife. A magnificent new library is being built directly opposite within the next two years.
"The arrival of recognised torchbearers, like City Loft Developments, marks the start of a new chapter of growth and prosperity after achieving city status."
There will be 80 homes, 20 of them low-cost. The scheme also includes workshops, shopping, offices, a restaurant and space for the Brighton Festival fringe.
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