A six year study of the country's coastal waters concluded that only 350 to 500 great white sharks remain.
This is half the level previously thought, the researchers from Stellenbosch University said.
The team said trophy hunting, pollution, shark nets and baited hooks were among the reasons for the decline.
"The numbers in South Africa are extremely low," said head researcher Sara Andreotti.
"If the situation stays the same, South Africa's great white sharks are heading for possible extinction."
The study, the largest of its kind in South African waters, was carried out in the Gansbaai area near Cape Town, a popular cage shark diving spot, and along the country's coastline.
Researchers were able to track the sharks by collecting biopsy samples and photographs of the dorsal fins, whose unique markings served as "shark fingerprints".
"We have come to the conclusion that South Africa's white sharks faced a rapid decline in the last generation and that their numbers might already be too low to ensure their survival," Ms Andreotti said.
The study will now form the first ever database of the country's shark population.
Despite the situation in South Africa, great white sharks can still be found in large numbers in Canada, Australia and the United States.
Prof Conrad Matthee, Stellenbosch University
"If we take sharks out of the eco system it is a cascade effect of the whole eco system that may collapse. And that is a serious problem for the eco system services that the marine environment give to humans"
South Africa's great white shark population is heading for possible extinction after a rapid decline in numbers, say researchers.