According to the latest figures collated by Johns Hopkins University, the US has overtaken China (81,782 cases) and Italy (80,589).
But with 1,200 Covid-19-related fatalities, the US death toll lags behind China (3,291) and Italy (8,215).
The grim milestone came as President Donald Trump predicted the nation would get back to work "pretty quickly".
How did the White House react?
Asked about the latest figures at a White House briefing on Thursday afternoon, President Trump said it was "a tribute to the amount of testing that we're doing".
Vice-President Mike Pence said coronavirus tests were now available in all 50 states and more than 552,000 tests had been conducted nationwide.
Trump says US tested more than S Korea - is he right?
Mr Trump also cast doubt on the figures coming out of Beijing, telling reporters: "You don't know what the numbers are in China."
He said he would speak to President Xi Jinping by phone on Thursday night, but denied the Chinese leader had asked him to "calm down" the language he uses to refer to the pandemic, which the US leader refers to as "the Chinese virus".
Does the president still hope to ease restrictions?
Mr Trump has set a much-criticised goal of Easter Sunday, 12 April, for reopening the country. That plan seemed to gather impetus on Thursday as it emerged an unprecedented 3.3 million Americans have been laid off because of the virus.
Media captionCoronavirus: Millions of Americans unemployed
At Thursday's briefing, he said: "They [the American people] have to go back to work, our country has to go back, our country is based on that and I think it's going to happen pretty quickly.
"We may take sections of our country, we may take large sections of our country that aren't so seriously affected and we may do it that way."
He added: "A lot of people misinterpret when I say go back - they're going to be practising as much as you can social distancing, and washing your hands and not shaking hands and all of the things we talked about."
He promised more details next week.
What could he be planning?
In a letter to state governors on Thursday, Mr Trump said his team plans to release federal social distancing guidelines that may advise some regions to loosen restrictions.
Mr Trump wrote of a "long battle ahead" and said "robust" testing protocols might allow some counties to lift their safeguards against the coronavirus.
He said the "new guidelines" would create low, medium and high risk zones that would allow the government to advise on "maintaining, increasing, or relaxing social distancing and other mitigation measures they have put in place".
Trump knows economic meltdown brings political pain
What this crisis reveals about US - and its president
The plan emerged as new research on Thursday estimated Covid-19-related deaths in the US could top 80,000 over the coming four months.
As many as 2,300 patients could die every day during the epidemic peak, set for some point in April, even if people observe strict social distancing, according to the study from the Institute for Health Metrics and Evaluation at the University of Washington's School of Medicine.
Can the president order everyone back to work?
No. Earlier this month, he set a 15-day period to slow down the spread of Covid-19 by urging all Americans to drastically scale back their public interactions.
But those guidelines were voluntary and did not amount to a national order.
The US Constitution makes clear states have the power for maintaining public order and safety, which scholars say means it is the responsibility of governors to decide when virus-related restrictions get lifted.
Currently 21 US states have told residents to stay in their homes in order to contain the pandemic.
What's happening elsewhere in the US?
In other developments:
Canada has condemned a US proposal to deploy troops along their joint border to help fight the spread of coronavirus, with the deputy prime minister saying it would be an "entirely unnecessary step which we would view as damaging to our relationship"
A supermarket in Pennsylvania said it had to destroy more than $35,000 worth of food after a woman intentionally coughed all over it in a coronavirus prank. The local prosecutor said it would decide whether or not to press charges once the suspect had been tested for the illness
According to the San Francisco Chronicle, coyotes are being seen roaming the empty streets of the California city, where residents have withdrawn behind closed doors to limit the spread of the virus