South Africa says non-citizens arriving from Ebola-affected areas of West Africa will not be allowed into the country.
The health ministry said borders would be closed to all non-citizen travellers from Guinea, Liberia and Sierra Leone.
South African nationals will be allowed to re-enter the country when returning from high-risk countries, but will undergo strict screening.
All non-essential outgoing travel to the affected countries has been banned.
Usual screening procedures are in place for those who travel between Nigeria, Kenya and Ethiopia, which have been defined as medium-risk countries.
South Africa has experienced two Ebola scares in recent weeks, involving passengers arriving from Liberia and Guinea. But the country has managed to stay Ebola-free until now.
Johannesburg has one of the major transit airports, connecting southern Africa with the rest of the continent.