The US Food and Drug Administration has authorised the Pfizer-BioNTech coronavirus vaccine for emergency use.
The agency said the authorisation was a "significant milestone" in the pandemic, which taken more than 295,000 lives in the US.
The vaccine, which offers up to 95% protection against Covid-19, was deemed safe and effective by the FDA.
President Donald Trump said the first vaccinations will take place "in less than 24 hours".
"Today our nation has achieved a medical miracle," Mr Trump said. "We have delivered a safe and effective vaccine in just nine months."
Before the announcement on Friday night, the FDA had come under intense pressure from the Trump administration to approve the vaccine's use.
The head of the agency, Stephen Hahn, was told to approve it for emergency use by Friday or quit, US media reported, although he called this "untrue".
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 already received regulatory approval in the UK, Canada, Bahrain and Saudi Arabia. Like those countries, the US will give its first doses of the vaccine to the elderly, health workers and emergency crew.
Coronavirus deaths have been rising sharply since November in the US. On Wednesday, the country recorded more than 3,000 deaths - the highest total in a single day anywhere in the world.