Joe Biden has spent 50 years in politics working towards this moment, but he could never have expected such huge challenges would be facing him on his first day at the helm. What are his priorities?
He'll get started with a 10-day flurry of executive orders.
These are presidential directives that don't require congressional approval.
Top of the list are rescinding a controversial travel ban, imposed by his predecessor Donald Trump against countries he viewed as a security threat, and rejoining the Paris climate deal.
Here's what else we know about what will demand the new president's immediate attention.
Coronavirus pandemic relief
Masking up America
The coronavirus has killed more than 400,000 people in the US - and the pandemic and its wide-ranging impact will be the new administration's top priority.
Mr Biden has called it "one of the most important battles our administration will face" and has vowed to implement his Covid strategy straight away.
One of his first moves will be executive action requiring social distancing and the wearing of masks on federal property nationwide and by federal employees and contractors.
Still, there's no guarantee the state governors who've so far opposed mask mandates will suddenly change their minds - there appears to be no legal authority that grants a president the power to bring in a nationwide mask rule.
Mr Biden seems to have conceded that point, and says he'll personally try to persuade governors to come around.
If they're not receptive, he's vowed to make calls to mayors and municipal officials to recruit them to the cause. There's also no word yet on how a mandate will be enforced.
100 million vaccine doses in 100 days
Mr Biden wants to speed up the vaccine rollout with the ultimate goal of vaccinating 100 million people with at least a first dose against Covid in his first 100 days in office.
One part of the acceleration plan is to release all available vaccine doses instead of holding some in reserve for the necessary second jab.
He is also expected to take executive action on efforts to develop and deploy rapid testing and to put in place a national supply chain for equipment, medications and personal protective equipment, or PPE.
On his agenda is a pledge to reverse the decision to have the US leave the World Health Organization (WHO).
Mr Trump announced plans over the summer to pull the country out of the WHO, accusing it of mismanaging Covid after the virus emerged in China and saying it failed to make "greatly needed reforms".
Relief for renters and homeowners
Mr Biden's team has said he has immediate plans to extend a moratorium on evictions and on foreclosures on home mortgages - both of which were paused early in the pandemic - as well as the current pause on federal student loan payments and interest.
Mr Biden's transition team said he plans to direct Cabinet agencies this week to "take immediate action to deliver economic relief to working families", though they did not offer more detail.
$1.9tn for the US coronavirus economy
Last week, Mr Biden announced a $1.9tn (£1.4tn) stimulus plan for the coronavirus-sapped US economy, saying that "a crisis of deep human suffering is in plain sight and there's no time to waste".
If passed by Congress, it would include direct payments of $1,400 to all Americans. He has also included funding to help schools safely reopen, which he wants to happen in the first 100 days.
It'll be in addition to a long-awaited $900bn stimulus package Congress passed in December, which Mr Biden had called a "down payment" on the larger proposed package.
Republicans lawmakers are likely to object to parts of the bill, which will add more debt to what the US has already spent dealing with the pandemic - and Mr Biden will need bipartisan support for the plan.
Democrats currently control both chambers of Congress, but only by narrow margins.
Ending Trump tax cuts
Covid aid isn't the only priority on the incoming president's economic agenda. He has pledged to get rid of Mr Trump's signature tax cuts as soon as he takes office.
Mr Trump passed the cuts in 2017, early in his presidency, and the Biden team says they unfairly reward the wealthiest Americans and favour corporations over small businesses.
Mr Biden has also said he would swiftly double the taxes that US firms pay on foreign profits - part of his Made in America push - which would come in addition to a rise in corporate taxes.
His tax policy legislation will need to pass Congress.
Environment and climate change
Back in the Paris Agreement
Another move Mr Biden says he will make on his first day in office is to rejoin the Paris climate agreement, a global accord that includes the goal to keep temperatures below 2.0C (3.6F) above pre-industrial times and "endeavour to limit" them even more, to 1.5C.
His predecessor pulled the US out of the 2015 accord - it became official on 4 November - making it the first nation in the world to do so.
The US will officially be part of the agreement again within 30 days.
Mr Biden has also pledged to "up the ante" and aim for higher standards on climate mitigation measures, and to convene a climate world summit within the first 100 days in office.
Mr Biden has said he wants to work with Congress to enact legislation this year that will allow the US to reach net-zero emissions by 2050.
Cancelling Keystone XL pipeline
In a move that has already sparked alarm with his northern neighbours, Mr Biden is reportedly planning to immediately rescind the cross-border permit for the controversial Keystone XL pipeline, a planned project from the oil sands of Canada's Alberta province, through Montana and South Dakota, to rejoin an existing pipeline to Texas.
Roll back deregulations
A further agenda item is a U-turn on much of Mr Trump's legacy of climate and energy deregulation, like the easing of vehicle emissions targets.
Mr Biden has said he will negotiate "rigorous" new emissions limits on cars and heavy-duty vehicles, to conserve 30% of US lands and waters by 2030, to ban new drilling on public lands, and to close the Arctic National Wildlife Refuge to drilling.
The new administration says it plans also to bring in "aggressive" methane pollution limits for oil and gas operations and to ban new oil and gas leasing on public lands and waters.
Scrapping the travel ban
The travel ban, signed by Mr Trump just seven days after taking office in January 2017, will be among the first policies to be discarded.
The ban initially excluded people from seven majority-Muslim countries, but the list was modified following a series of court challenges.
It now restricts citizens of Iran, Libya, Somalia, Syria, Yemen, Venezuela and North Korea.
A pathway to citizenship
In another major immigration pledge, Mr Biden has said he'll swiftly send a bill to Congress laying out a pathway to citizenship for over 11 million undocumented immigrants.
"And all of those so-called dreamers, those Daca [Deferred Action for Childhood Arrivals programme] kids, they're going to be immediately certified again to be able to stay in this country and put on a path to citizenship," he said in late October.
Late in the election, the campaign announced Mr Biden would create a task force to reunite some 545 migrant children separated from their parents at the US southern border.
In December, the Biden team conceded it would need more time to roll back one of Mr Trump's policies, the Migrant Protection Protocols that force thousands of asylum seekers to wait in Mexico for US immigration court hearings.
Once a "Day One" pledge, officials now say it could take about six months to address.
Ending border wall construction
Mr Biden has vowed to halt construction of a project synonymous with Mr Trump's presidency - the border wall between the US and Mexico. His campaign had called it "a waste of money" that "diverts critical resources away from the real threats".
The administration says it will instead divert the federal funds towards efforts like new border screening measures.
Race and criminal justice reforms
The national reckoning with race is the fourth crisis - alongside Covid, the economy and climate - Mr Biden says he must tackle quickly.
Some of those policies - like addressing racial disparities in housing and healthcare - overlap with his other plans.
Mr Biden will sign an executive order on racial equality and call on all US agencies to create a plan to tackle any unequal barriers to opportunity. It will also rescind Mr Trump's executive order limiting the ability of federal government agencies to implement diversity and inclusion training.
Mr Biden has promised to set up a national police oversight body to assist in reforming police departments in his first 100 days in office, though details of that plan are scarce.
He has said he wants swift passage by Congress of the "Safe Justice Act", which includes measures on reforming mandatory minimum sentences and increasing funding for community based policing.
He has made commitments to the LGBT community as well, like directing resources towards helping prevent violence against transgender people, ending the ban on transgender people serving in the military, and restoring guidance for transgender students in schools.
One other priority is passing the Equality Act, which would add sexual orientation and gender identity to existing federal civil rights laws, though how fast he can pass that legislation remains unclear.
Reassuring US allies
The incoming president says he plans to quickly reach out to US allies to smooth ruffled feathers and promise that "America has your back", saying the US must "prove to the world that [it] is prepared to lead again - not just with the example of our power but also with the power of our example".
He has said on his first day in the Oval Office he would reach out to Nato allies with the message "we're back and you can count on us again".
Though Mr Trump was not the first president to pressure other North Atlantic Treaty Organisation members to spend more on defence, he threatened at times to withdraw from the alliance that Mr Biden has called the "bulwark of the liberal democratic ideal".