The Navy ship has sat largely empty off the west side of Manhattan as hospitals have remained swamped.
On Monday, the Trump administration reached a deal with Governor Andrew Cuomo to allow COVID-19 patients on board.
President Donald Trump said he agreed to the change after speaking with Cuomo.
"We hadn't had that in mind at all, but we're going to let him do that and we're also going to let New Jersey. Hopefully that will be very helpful to both states," President Trump said.
"As a nation, this is plain truth time, there's no political nuance, there's no spin. People are dying, everybody has a role to play."
The ship has beds for up to 1,000 patients, but so far has treated just 41 people, officials said, in part because of strict screening rules.
The floating hospital was brought to New York with the intent that it relieve pressure on city hospitals by treating people who had health problems, but were COVID-19 free.
Jonathan Hoffman, chief spokesman for the Department of Defense, said the preference still is to have virus patients go to a temporary hospital set up in the nearby Jacob K. Javits Convention Center.
But emergency patients will now be seen on the ship, whether or not they have the virus.
Air Force Brig. Gen. Paul Friedrichs, the Joint Staff surgeon, said the Comfort has the capacity to isolate only a "small number" of patients with the virus.
A non-medical crew member on board the USNS Comfort has tested positive for COVID-19 before they ever started taking any coronavirus patients, suggesting that person boarded the ship with the illness before it ever made it to New York.
Also, an additional 1,500 military medical personnel will be in New York City by Wednesday. Of those, more than 350 are going to 11 city hospitals to help supplement overwhelmed medical staff.
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