Police said the long-distance bus traveling from the rural Eastern Cape to Cape Town was carrying about 50 people when it crashed and rolled outside the town of Aberdeen, the SAPA news agency reported.
"There were six females, four males and one child killed," a police inspector told the news agency.
"About 30 passengers were slightly injured, but five are in a serious condition. The driver was not hurt."
South Africa's roads are among the most dangerous in the world and road accidents kill about 10,000 people every year.