Joe Biden is projected to win the election and become the 46th president of the United States.
After a nail-biting race, the Democratic candidate took an unbeatable lead in Pennsylvania – picking up its 20 Electoral College votes and passing the 270 needed to gain the White House.
It makes Donald Trump the first one-term president since 1992, when George HW Bush failed to clinch four more years.
Celebrations have broken out on the streets in several states, with people dancing and cheering. One jubilant supporter declared “we made history”, while another said: “I’m proud to be an American again.”
Mr Trump refused to concede the election and in a written statement released by the campaign accused his opponent of “rushing to falsely pose as the winner”.
“Beginning Monday, our campaign will start prosecuting our case in court to ensure election laws are fully upheld and the rightful winner is seated,” he added.
“I will not rest until the American people have the honest vote count they deserve and that democracy demands.”
But three days and 16 hours after the first polls closed, president-elect Mr Biden has accepted victory and announced in his first public comments that “democracy beats deep in the heart of America”.
“With the campaign over, it’s time to put the anger and the harsh rhetoric behind us and come together as a nation,” he said.
“It’s time for America to unite. And to heal. We are the United States of America. And there’s nothing we can’t do, if we do it together.”
He is expected to make a TV address at 1am (8pm ET) on Saturday and it is reported that he will set up a 12-member coronavirus taskforce on Monday.
Jill Biden, the future first lady, posted a photo of her and her husband celebrating, holding a sign where she covered up the word “vice”.
Mr Biden’s path to power looked in doubt when he failed to make early, convincing gains in areas like Ohio, Texas and Iowa on election night.
And while counting continued, Mr Trump made incendiary claims about ballot stuffing and accused his opponents of “fraud” – without providing any evidence.
He even tried to claim victory early, declaring in an address to the nation from the White House: “We will win this and as far as I’m concerned we already have won it.”
But Mr Biden, who will be the oldest sitting president ever, urged supporters to “keep the faith” and wait until all votes had been counted.
“We the people will not be silenced; we the people will not be bullied; we the people will not surrender,” he said.
As the hours wore on, Mr Biden finally started gaining ground – and flipped the first red state to blue in Wisconsin.
The former vice-president to Barack Obama went on to take Michigan, Pennsylvania and Nevada, and is ahead in Arizona and Georgia, where votes are still being counted and are too close to call.
Mr Trump, who is leading in undeclared Alaska and North Carolina, has said he may contest Mr Biden’s White House win in the Supreme Court.
World leaders have already begun welcoming Mr Biden’s win, with Prime Minister Boris Johnson tweeting: “Congratulations to Joe Biden on his election as president of the United States and to Kamala Harris on her historic achievement.
“The US is our most important ally and I look forward to working closely together on our shared priorities, from climate change to trade and security.”
Canadian Prime Minister Justin Trudeau also said: “Congratulations, Joe Biden and Kamala Harris. Our two countries are close friends, partners, and allies.
“We share a relationship that’s unique on the world stage. I’m really looking forward to working together and building on that with you both.”
Mr Obama hailed the “historic and decisive victory” and urged all citizens to give the president-elect “a chance and lend him your support”.
He warned “the country remains deeply and bitterly divided”, so Americans should “lower the temperature and find some common ground”.
Hillary Clinton, who lost against Mr Trump in 2016, also tweeted: “It’s a history-making ticket, a repudiation of Trump, and a new page for America. Thank you to everyone who helped make this happen. Onward, together.”
Kamala Harris, the new vice president-elect, released a video of the moment she spoke to Mr Biden on the phone about their historic win.
She will be the first black woman and Asian-American ever to be number two in the White House, as her father is Jamaican and her mother was Indian.
Analysis: How Joe Biden paved his path to power – and what comes next for divided America
By Cordelia Lynch, US correspondent
Joe Biden has done what Democrats nominated him to do – win back the Rust Belt to win back the White House.
He did it by getting back the white voters who deserted the Democratic Party four years ago.
Among them, some of the non-college educated voters that couldn’t find it in themselves to vote for Hillary Clinton.
But much more critical to his success were the college educated voters in the suburbs and densely populated cities; Mr Biden is the beneficiary of demographic change.
Back in March in the South Carolina primary, it was black voters that helped secure his nomination when he was struggling.
Eight months later, it is black voters in Philadelphia, Detroit and Milwaukee who have helped push him over the line once again.
With it, Mr Biden achieved something monumental – more votes than any presidential candidate in US history, passing the 69.4 million record that Barack Obama set in 2008.
At a time of unprecedented discord, his call for unity, stability and civility resonated.
But it wasn’t a landslide and while Democrats retain control of the House they suffered some critical losses.
The control of the Senate also hangs in the balance. Without it, passing legislation will be very, very challenging.
Can bi-partisan Mr Biden work with the other side in such a divided climate? The answer to that will define his presidency.