More than 800 people were evacuated when a main water supply pipe burst on Monday in Mamelodi, east of Pretoria, Tshwane emergency services said.
Spokesman Johan Pieterse said the Phomolong informal settlement was flooded when the pipe burst at around 1am on Monday.
"We are still busy on the scene with a search and rescue mission as some of the people were missing family members."
He said one person was taken to hospital in a critical condition while five others sustained minor injuries.
"The Hans Strijdom drive have been closed from the Hinterland Avenue to the Pretoria Avenue. Traffic will be affected as the road will only be opened much later on Monday."
Motorists were advised to take alternative routes.
Pieterse said they would soon know which suburbs have been affected with water supply.