The mass shooting shortly late on Tuesday in an informal settlement in the Cleveland suburb of Johannesburg had the hallmarks of organised crime gangs vying for control of illegal mining or other activities, though police said the motive was still under investigation.
Police said the shooters were dropped off at the settlement in a minibus "and moved through the area, opening fire on residents and community members at multiple locations before fleeing the scene in the same vehicle".
The victims were nine men and three women, according to police, with 11 dying at the scene and another victim dying in hospital.
A manhunt was launched for the suspects and no arrests had been made, police said.
Informal settlements in South Africa are unplanned residential areas that are common in and around big cities where people looking for housing live in shacks or other makeshift structures.
South Africa has seen several high-profile mass shootings recently, including two in December that killed more than 20 people.
One of those attacks also involved multiple shooters.
Mass shootings in South Africa are often connected to criminal gangs.
In Johannesburg, violent gangs are involved in illicit mining in and around a city that has large gold reserves and many mines that have been abandoned by companies.
They are renowned for fighting violent turf wars with rival gangs or other killings to try to reinforce their control of areas.
Cleveland is a suburb connected to illegal mining activity, local councillor Neuren Pietersen said in an interview with local media, though he added there were also other problems in the area and it was not certain illegal mining gangs were responsible for the killings.
Police deployed specialist crime intelligence officers to the scene.
Provincial police commissioner Tommy Mthombeni said the attackers were "heartless" but refused to link the killings to illegal mining until the investigation was complete.
South Africa has extremely high violent crime rates, with the country recording more than 23,000 homicides in the past financial year, according to official crime statistics, an average of more than 60 a day.
