Wickets tumbled in the first hour of the day as Dale Steyn, the chief destroyer, walked away with 6/34.
Rita Jeptoo, winner of the Boston and Chicago marathons, has tested positive for a banned substance.
Opener Cook, who has been woefully out of form with the bat, will be replaced as skipper.
The tourists are 76 for two in their second innings, still 275 runs away from making the Proteas.
Kaizer Chiefs will be looking for their 14th win of the season when they host Mpumalanga Black Aces.
The Western Province Rugby Union yesterday announced its intention to remain at Newlands.