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.
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".