Seven females and three males were killed when their home near the city of Pietermaritzburg was ambushed early on Friday morning, according to BBC.
Police Minister Bheki Cele said two suspects had been arrested, one was shot dead and another is still at large. The motive is unclear.
Police were first alerted to the shooting after neighbors heard gunshots.
Mr. Cele said one of the victims was as young as 13, adding: "It's a crime scene, terrible. Too many people were lost here."
"They have arrested two people, one was injured, one is dead, one ran away and three firearms were recovered," he told reporters at the scene of the shooting in the township of Imbali in eastern KwaZulu-Natal province.
One child has reportedly been taken to hospital.
South Africa has one of the world's highest murder rates.
It's the second mass shooting in KwaZulu-Natal province this week after four people were shot and killed on Thursday at another home north of the port city of Durban.
In January, eight people were shot dead at a birthday party in Gqeberha city in Eastern Cape Province. It followed a string of gun attacks in bars last year, with at least 15 killed in one shooting alone.
SKH/PR