Police said seven women and three men were fatally wounded in Imbali, a township south of Pietermaritzburg in the southeastern province of KwaZulu-Natal.
“According to initial police reports, unknown gunmen stormed a Pietermaritzburg homestead and ambushed the family,” police spokeswoman Lirandzu Themba said in a statement.
The motive for the killing was not immediately clear.
Police Minister Bheki Cele was due to visit the crime scene.
Mass shootings are relatively common in South Africa, which has one of the world's highest murder rates.