The outgoing president's handling of the crisis has received harsh criticism.
The running total of lives lost, as compiled by Johns Hopkins University, is nearly equal to the number of Americans killed in the Second World War.
It took four months to reach the first 100,000 dead, but took just over one month to go from 300,000 to 400,000.
The number of dead in the US is about the population of New Orleans and equivalent to the crowd that was at Woodstock in 1969.
It is just short of the estimated 409,000 Americans who died in 2019 of strokes, Alzheimer’s, diabetes, flu and pneumonia combined.
The virus is still raging across many areas of the US and like in the UK, the country is facing a tough few weeks.
A widely cited model by the University of Washington projects the death toll will reach nearly 567,000 by May 1.
While the Trump administration has been credited with Operation Warp Speed, the programme to develop and distribute coronavirus vaccines, President Trump has repeatedly downplayed the threat, mocked mask-wearing and railed against lockdowns.
His complaints about suppression tactics often undermined statements made by leading US health officials and led to confused messaging from the top.
On top of this the wrangling over the various relief bills passed by Congress often led to delays hitting many American's, who were already suffering hard.
The White House defended the administration.
“We grieve every single life lost to this pandemic, and thanks to the president’s leadership, Operation Warp Speed has led to the development of multiple safe and effective vaccines in record time, something many said would never happen,” said White House spokesperson Judd Deere.
The first known deaths from the virus in the US were in early February 2020, both of them in Santa Clara County, California.
While the count is based on figures supplied by government agencies around the world, the real death toll is believed to be significantly higher, in part because of inadequate testing and cases inaccurately attributed to other causes early on.
President-elect Joe Biden takes office on Wednesday and has promised 100 million vaccines in his first 100 days.
He also hopes to pass another substantial coronavirus relief bill to help struggling citizens and businesses.
Mr Biden, took part in an evening ceremony on Tuesday near the Lincoln Memorial in Washington to honor the 400,000 dead.
Michigan Covid nurse Lori Marie Key sings Amazing Grace at memorial to remember coronavirus victims
The bell at the Washington National Cathedral was set to toll 400 times. Other cities around the US planned tributes as well.
The US accounts for nearly 1 of every 5 virus deaths reported worldwide, far more than any other country despite its great wealth and medical resources.