The Civil Aviation Authority granted the airline permission for the flight, which is due to take place from London Heathrow to New York JFK on November 28.
The permit was awarded following a number of technical reviews by the UK regulator, including the successful ground testing of the Rolls-Royce Trent 1,000 engine that powers Virgin's 787 aircraft using 100 per cent Saf.
Virgin must now seek permission from regulators in the US, Ireland and Canada for the flight.
Saf is produced from sources such as green hydrogen, agricultural waste and used cooking oil.
It can cut carbon emissions by up to 70 per cent compared with traditional jet fuel but is much more expensive to produce.
Saf accounted for only 0.5 per cent of aviation fuel in 2021 but many airlines have a target of using it for 10 per cent of flights by 2030 and the industry's goal of "net-zero" emissions by 2050 relies on Saf accounting for 65 per cent of fuel.
Virgin said it hoped the transatlantic flight would highlight the need to make Saf more readily available.
Saf is currently only made in small volumes and costs between three to five times as much to produce as regular jet fuel.
"We're committed to using 10 per cent Saf by 2030 but to get there we need the government to support the creation of a UK SAF industry," said Virgin Atlantic chief executive Shai Weiss.
Saf can currently be used in jet engines to a maximum blend of 50 per cent with kerosene, without the need for modifications.
CAA chief executive Rob Bishton said: "As the UK's aviation regulator, it's important that we safely enable the industry to embrace more sustainable practices and push the boundaries of what's possible to create a greener aviation industry.
"This permit not only allows Virgin Atlantic and others to showcase their commitment to sustainability but also serves as an example of how the industry is always exploring new technologies.
"Innovation and sustainability are vital areas of work but they must go hand-in-hand with safety.
"This is a reminder that together we can drive change, reduce emissions and make the skies greener for generations to come."
The first Emirates flight to run on Saf took off from Dubai International Airport on October 24 bound for Sydney. It was powered by 40 per cent Saf and 60 per cent conventional jet fuel.
Emirates says the chemical characteristics of this ratio are identical to conventional jet fuel and can be integrated seamlessly with no modifications required.
Last week the World Travel and Tourism Council's (WTTC) chief on Thursday urged governments to provide incentives for companies to produce saf on a wider scale to reduce the sector's carbon footprint.
Transport makes up 40 per cent of the travel and tourism sector's greenhouse gas emissions, out of which 36 per cent comes from international aviation and two thirds from domestic flights and ground transport, according to the WTTC.