The men were about to be transported back to Johannesburg prison, following their court appearance on Wednesday, Lieutenant-Colonel Lungelo Dlamini said.
"The suspects escaped while they were being loaded into a police truck, by overpowering the police officers and the court guards. They were appearing in court for various serious and violent crimes, including robbery and murder."
Anyone with information about their whereabouts could contact Crime Stop on 08600 10111.
Information about one of the escapees, Sibusiso Hamilton Mabuza, should be forwarded to Colonel Wiseman Sephungu on 071 363 3730.
Sephungu is investigating a business robbery and murder case against him.
Mabuza should be considered armed and dangerous.
A reward has been offered for information leading to the arrests of any of the men.