The development comes on the heels of rising cases of cholera in Southern Africa, with Malawi battling its deadliest outbreak yet, with more than 1,300 deaths.
Cholera can cause acute diarrhoea, vomiting and weakness and is mainly spread by contaminated food or water. It can kill within hours if untreated.
The two new cases in South Africa are of men in their 20s who had no travel history, the health department said, adding one of them has subsequently died.
"One of his contacts is still in hospital and further investigation is being conducted," it said in a statement.
South Africa reported two imported cases of the disease from Malawi earlier this month. The husband of one of the first two cases also later tested positive.
While cholera is not endemic in South Africa, health officials have called for vigilance and hygiene amid fears of local transmission of the disease.
Malawi's neighbours Mozambique and Zambia have also reported cholera cases, while Ethiopia, Kenya and Somalia in the East are responding to outbreaks amid a terrible and protracted drought.
In West and Central Africa, there have been cases in Cameroon, Democratic Republic of the Congo and Nigeria.
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