The US Food and Drug Administration has authorised the Pfizer BioNTech coronavirus vaccine for emergency use.
The agency had come under intense pressure from the Trump administration to approve the vaccine's use.
FDA head Stephen Hahn was told to approve it on Friday or quit, US media said, although he called this "untrue", reports BBC.
President Donald Trump says the first vaccinations will take place "in less than 24 hours". The virus has now killed more than 292,000 in the US.
Health and Human Services Secretary Alex Azar, told reporters earlier on Friday that his department would work with Pfizer to get the mass vaccination programme started by Monday or Tuesday.
The Pfizer vaccine has received regulatory approval in the UK, Canada, Bahrain and Saudi Arabia.
On Wednesday, the US recorded more than 3,000 deaths - the highest total in a single day anywhere in the world.
What has the FDA said?
On Thursday, medical experts advising the FDA recommended the emergency-use approval. A 23-member panel concluded the vaccine's benefits outweighed its risks.
"Following yesterday's positive advisory committee meeting outcome regarding the Pfizer-BioNTech Covid-19 vaccine, the US Food and Drug Administration has informed the sponsor that it will rapidly work toward finalisation and issuance of an emergency use authorisation," the FDA statement said.
"The agency has also notified the US Centers for Disease Control and Prevention and Operation Warp Speed [the federal government's vaccine distribution programme], so they can execute their plans for timely vaccine distribution."
What could happen now it has been approved?
Operation Warp Speed says that vaccine deliveries will begin within 24 hours of approval.
Mr Azar said the US would work with Pfizer to get the vaccine shipped out so that it could be administered to the most vulnerable people by Monday or Tuesday.
Pfizer plans to have 6.4 million doses ready for the US in its first rollout round in late December.
Because two injections are required per person, that is enough for three million people, out of a total US population of 330 million.