Donald Trump says healthy Americans will now be able to return to work as conditions allow, but must maintain social distancing and stay home if they are sick.
During his daily press conference on Thursday, Trump said governors will be empowered to tailor the White House guidelines to their own states - and if they need to remain closed his government will "allow them" to do that.
Those that meet the criteria can begin the process as early as today as per a new plan called "Opening up America".
"We are not opening all at once, but one careful step at a time," he said, adding that states are encouraged to work together to harmonise their regional efforts.
"A prolonged lockdown combined with a forced economic depression would inflict an immense and wide-ranging toll on public health," Trump said, adding it could lead to a sharp rise in drug abuse, alcohol abuse, suicide, heart disease."
US coronavirus deaths went above 33,000 on Thursday, according to a Reuters tally, with fatalities rising by nearly 2,200 - and some states are yet to report.
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This comes after a record single-day increase of 2,507 on Wednesday.
Washington's goal is to quickly identify future outbreaks and put them out rapidly, with the president going on to promise testing capacity will continue to be expanded.
The new federal guidelines recommend that states record a 14-day "downward trajectory" in coronavirus cases before beginning a three-phase process of re-opening.
Before states re-open, hospitals should have a "robust testing program" that includes antibody testing in place for healthcare workers, the guidelines say.
Mr Trump said if the virus returns in the autumn, these new guidelines will ensure the country is up and running and able to put a second wave out quickly.
He added that America must be extra vigilant to block the virus from entering the US from abroad.
In the first phase of re-opening, the guidelines say groups of more than 10 people should be avoided if appropriate distancing measures are not practical.
Non-essential travel could resume and schools could open their doors again during phase two.
In phase three, medically vulnerable people could resume public interactions.
The new guidelines come on the same day as governors of New York and six other northeastern states extended their coronavirus stay-at-home orders to May 15.
The governors have cited the apparent success of their social-distancing directives in curbing the spread of the virus, which has killed more than 32,600 Americans in a matter of weeks, while acknowledging they have wreaked economic havoc.
At least 650,000 people to date have tested positive in the United States for COVID-19, the highly contagious lung disease caused by the virus.
A total of 42 states have ordered residents to remain indoors except for necessary outings, such as grocery shopping or doctors visits, while closing schools, universities and non-essential businesses.
The unprecedented measures have strangled large swaths of the economy, idling at least 20 million workers, upending financial markets and leading to forecasts that America is headed for its deepest recession since the economic collapse of the 1930s.
Trump, who has staked his November re-election bid on the strength of the US economy, has pushed for a May 1 restart of shuttered commerce - at least in regions least stricken by the pandemic - despite health experts' warnings that doing so prematurely risks reigniting the outbreak just as it was being brought under control.
The debate over how and when to reopen the economy has led to growing friction between the Republican president and political leaders in the hardest-hit states, particularly Democratic governors whom he branded as "mutineers."
Senior White House officials told Reuters that Trump's new set of reopening guidelines were backed by medical experts on his coronavirus task force.
The plan includes recommendations on when bars and restaurants, as well as sporting events and other large public gatherings should resume, the officials said.
The recommendations are data driven and incorporate "certain medical-based metrics" that allow local authorities on a county-by-county basis to determine "where they fit," one official said.
On Thursday, Cuomo and six East Coast counterparts who formed a regional pact this week to coordinate economic reopenings in their states - New Jersey, Connecticut Pennsylvania, Delaware, Massachusetts and Rhode Island -announced their existing restrictions would remain intact through the middle of next month.
"What happens after that, I don't know - we will see depending on what the data says," Cuomo, whose state is the US epicenter of the global coronavirus pandemic, accounting for 40% of the country's dead, said at a news briefing.
The New York state extension was ordered even though key metrics such as the rate of new hospitalizations pointed to an ebbing of the outbreak there.
Public health experts say a major expansion of testing to determine the full scope of the pandemic, track new infections and gauge the extent of any "herd" immunity in the general population is necessary before social distancing restrictions can safely be relaxed.
Wisconsin Governor Tony Evers on Thursday extended his state's "safer at home" order until May 26, but carved out a new exemption for golf courses while extending curb-side pickup and delivery allowances to non-essential businesses.
Last week, Los Angeles, the nation's second-largest city, extended its restrictions to May 15, and the District of Columbia did likewise on Wednesday.
Missouri Governor Mike Parson on Thursday extended his "Stay Home Missouri" Order through May 3.
In addition to the seven-state East Coast coalition, the governors of California, Oregon and Washington state have vowed to work together on a West Coast reopening plan, and seven states in the Midwest on Thursday announced a similar alliance.
In the latest measure of the economic toll taken by the pandemic, another 5.2 million Americans sought unemployment benefits last week, the Labor Department reported on Thursday, lifting total filings for claims over the past month to more than 22 million.
"Really, there's no comparable event in American economic history," said Daniel Zhao, senior economist at Glassdoor recruiting site.
"This crisis combines the scale of a national, if not global, downturn with the pace of a natural disaster."
The number of known US infections rose by at least 30,000on Wednesday, the biggest increase in five days, according to a Reuters tally.
But not all states have been hit equally hard.
A handful of governors this week began talking about reopening their states as early as May 1, including North Dakota's Doug Burgum, Ohio's Mike DeWine, and Tennessee's Bill Lee.
Eighteen states have recorded fewer than 100 deaths from COVID-19.
Even within states, urban areas have been hit harder than rural areas.
That divide has inflamed political and social divisions and prompted protests against state leaders who opted to keep residents at home.
In Richmond, Virginia, about 30 people gathered outside the state Capitol on Thursday in defiance of a stay-at-home order that the Democratic governor has instituted until June 10.
"STOP the MADNESS! It's just a COLD VIRUS! End the shutdown for the GOOD of US all!" one of the demonstrators' signs read.
The state has recorded nearly 7,000 cases and 208 deaths.
