The vast temporary facility – set up in the city’s Central Conference Centre – will treat patients from across the north west who are recovering from the severest symptoms of Covid-19 but still in need of specialist care.
It will open its doors late next week, health chiefs in the city said on Thursday.
The action comes amid growing fears hospitals in Greater Manchester and the surrounding area could be overwhelmed by those suffering from the virus.
Watch: Will Greater Manchester’s intensive care units be overwhelmed?
Announcing the decision, Professor Jane Eddleston, medical director at Manchester University NHS Trust, said there were currently 95 Covid-19 patients in critical care in Greater Manchester.
And, while that is less than when the pandemic was at its peak in April – when there were 260 such patients – she said the centre would reduce pressure mounting on existing facilities.
"The Nightingale will not be used as a critical care facility and neither was it in the first phase, it will be used as a facility for patients to have additional rehabilitation,” she said.
David Regan, director of public health for Manchester, added that the decision had been taken as cases of older people contracting the illness continues to rise.
"Unfortunately, our older population are more at risk of developing complications from Covid which may result in hospital admissions,” he said.
The pair said other hospitals in the region had been made secure from coronavirus to ensure elective procedures can continue to take place.
Greater Manchester will be placed into the highest tier three of the government’s new coronavirus restrictions from a minute past midnight on Friday.
Watch: Which areas are in what tier in the UK?