Six of the victims were children, with the youngest just eight years old.
"We responded to the fire at about 2.20 am this morning," emergency services spokesman Robert McKenzie told AFP.
"Four more people were taken to hospital with injuries ranging from serious to mild. None were in a critical condition."
The fire tore through the boys' section of the orphanage and all those who died were males aged between eight and 21.
The blaze was extinguished about four hours later and the cause is being investigated.
That August, 22 elderly people died in a fire at a retirement home in Nigel on the southeastern outskirts of Johannesburg.
The following year in June, 12 residents of a home for the mentally disabled in the town of Springs east of Johannesburg were killed in an overnight fire.