Flights from the key tourist destination will be suspended from 12 noon on Friday.
The health secretary, Sajid Javid, said: “As part of our close surveillance of variants across the world, we have become aware of the spread of a new potentially concerning variant, which UKHSA has designated a ‘variant under investigation’.
“We are taking precautionary action to protect public health and the progress of our vaccine rollout at a critical moment as we enter winter, and we are monitoring the situation closely.”
Two British Airways overnight flights from London Heathrow, BA43 to Cape Town and BA55 to Johannesburg, took off shortly before the announcement was made.
Passengers will learn on arrival that they must go into hotel quarantine when they return at a cost of over £2,000.
A spokesperson for British Airways said: “Following the latest announcement from the health secretary we’re working through plans for our customers and colleagues currently in South Africa and those due to travel from the UK in the coming days.
“We’ll be contacting affected customers with information about their flight.”
Virgin Atlantic’s departure from Heathrow to Johannesburg has been delayed.
Namibia, Lesotho, Botswana, Eswatini and Zimbabwe will also be added to the red list. None has direct links with the UK.
UK scientists sounded the alarm on Thursday night over the B.1.1.529 variant, which has the potential to evade immunity built up by vaccination or prior infection.
While no cases have been found in Britain, officials raised concern over a rapid rise in cases in South Africa.
At the moment around 500 and 700 people are travelling to the UK from South Africa each day, but it is expected this figure could increase as the festive period begins.
The variant has not yet been given the title “variant of concern” in the UK, but one senior UK Health Security Agency (UKHSA) expert said: “This is the worst variant we have seen so far.”
Only 59 confirmed cases have been identified in South Africa, Hong Kong and Botswana.
The variant has over 30 mutations – around twice as many as the Delta variant – which could potentially make it more transmissible and evade the protection given by prior infection or vaccination.
The UK government announcement has been met with despair by the travel industry, as it mirrors the ban imposed on South African flights almost a year ago because of fears of what became known as the Beta variant.
Paul Charles, chief executive of the travel consultancy, the PC Agency, said: “Yet again the government is falling back on widespread country measures rather than assessing individual risk.
“There is currently no evidence that fully-jabbed citizens are at risk from this apparent new variant. So it seems a strange backward step to take.”
South Africa was effectively off limits to British travellers for almost a year. It was taken off the red list last month.