Earlier in the day, Dale Steyn continued his good form with the ball by picking up the wickets of Azhar Ali for a well-deserved 90, and the prize scalp of Younis Khan for just 14.
Spinner Paul Harris managed breakthrough wickets just after lunch, having Asad Shafiq caught by Jacques Kallis at first slip for 61, and after tea with Adnan Akmal caught by Hashim Amla for just 17.
Pakistan remains resilient though, with Misbah-ul-Haq and newcomer to the crease Abdur Rehman seeing out the day's play.
Scores at stumps:
South Africa 1st innings 584-9 dec (AB de Villiers 278 not out, J. Kallis 105; Tanveer Ahmed 6-120)
Pakistan 1st innings (overnight 59-1)
Mohammad Hafeez lbw b Steyn 2
Taufiq Umer c Amla b Kallis 43
Azhar Ali c Smith b Steyn 90
Younis Khan c Amla b Steyn 14
Misbah-ul-Haq not out 77
Asad Shafiq c Kallis b Harris 61
Adnan Akmal c Amla b Harris 17
Abdul Rehman not out 0
Extras: (b5, lb6, nb1, w1) 13
Total: (for six wkts, 106 overs) 317
Fall of wickets: 1-2 (Hafeez), 2-119 (Umer), 3-153 (Younis), 4-156 (Ali), 5-263 (Shafiq), 6-309 (Adnan)
Bowling: Steyn 24-7-78-3 (1w), Morkel 24-10-66-0 (1nb), Kallis 17-6-47-1, Botha 11-3-44-0, Harris 30-10-71-2
Toss: Pakistan
Umpires: Daryl Harper (AUS) and Asoka De Silva (SRI)
TV umpire: Nadeem Ghouri (PAK)
Match referee: Andy Pycroft (ZIM)