The first half of more than 5.6 million Pfizer vaccine doses have arrived in the country from the United States (US).
The plane carrying over 2.8 million vials touched down at OR Tambo International Airport on Saturday afternoon.
The health department said the doses would make their way to vaccine sites across the country next week.
The second batch is expected to arrive on South African soil by Tuesday.
President Joe Biden has started delivering on his promise that the US would donate vaccines to the world’s poorest nations.
The donation of 5, 66 million vaccines – which has been promised to South Africa – is the largest donation to a single country and has been made possible by the Covax facility which ensures low to middle-income countries are not left behind in efforts to vaccinate the globe.