The NHS Nightingale has admitted its first patients, according to a spokesperson for the hospital.
The facility was set up in east London's ExCeL Centre in just nine days and has added over 4,000 critical care beds to treat mainly younger sufferers.
Similar hospitals are in the pipeline across the UK, including in Cardiff, Glasgow, Manchester, Harrogate and Bristol.
A spokesperson for the hospital said: "There is also treatment capacity available in other hospitals across London to complement the care being provided at the London Nightingale".
The Prince of Wales officially declared the Nightingale open via video link from his Scottish home, saying it "offers us an intensely practical message of hope for those who will need it most at this time of national suffering".
The NHS Nightingale confirmed that is now operational and accepting patients to its site.
It wrote on Twitter: "This evening the @RoyalAirForce and @Ldn_Ambulance practiced a patient transfer. Speed and efficiency come naturally to our emergency responders #ThankYou for helping us to treat the people that need us, when they need us most."
More than 16,000 members of staff will be needed to run the facility when it reaches full capacity and members of the army worked 15-hour days so it is finished as soon as possible.
The Nightingale will become one of the biggest hospitals in the world, according to its chief operating officer Natalie Forrest.
Speaking to visiting reporters, Ms Forrest said a "scary" number of staff would be needed to run the facility at full capacity and appealed for volunteers to come forward.
"If we have to use this facility, which I really hope we don't because everyone is staying home and washing their hands and social distancing, we will need thousands of doctors and nurses and volunteers to run this facility," she said.
Asked to clarify how many are required, Ms Forrest said: "The numbers are scary, but if I tell you that to run one ward, including all of our ancillary staff, we need 200 members of staff."
The hospital will initially aim to care for 42 patients, before its expansion is "ramped up" to ensure it can meet its full 4,000-bed capacity in two weeks' time if needed, the Nightingale's chief medical director Alan McGlennan said.
While the Nightingale will be able to provide up to 4,000 ventilator beds if they are needed, NHS London will still have control over the "most precious resources", he added.
Eamonn Sullivan, the hospital's director of nursing, said the facility will be able to operate as a large intensive care unit or a normal ward, depending on demand.
The Nightingale will also include support services found in other NHS hospitals, such as pharmacies and therapy treatment, Mr Sullivan said.
Meanwhile, staff working at the Nightingale will be able to sleep at nearby hotels once they finish their shift, Mr Sullivan said.