Pakistan captain Inzamam-ul-Haq hit 92 not out to dampen the celebrations of Makhaya Ntini, who took his 300th wicket for South Africa in the second Test on Saturday.
South Africa were 115 for three in their second innings at the close of the second day, a deficit of 26 runs. Jacques Kallis was 50 not out with Ashwell Prince on 21.
Pakistan were dismissed for 265 in their first innings in reply to South Africa's 124.
Ntini, who took four wickets on Friday, reached his milestone in the eighth over of the day when he had Mohammad Sami caught behind by wicketkeeper Mark Boucher for 10.
The bowler celebrated by lifting his playing shirt to reveal a T-shirt which said "Mdingi Express 300".
"It's been a marvellous day, to take my 300th wicket at home was great," Ntini, who hails from the Eastern Cape village of Mdingi, told a news conference.
"Not all of us get to do that. It means more than anything to do it in front of your own people, in that atmosphere."
Ntini became the third South African to take 300 test wickets after the retired Allan Donald and team mate Shaun Pollock. He ended the innings with six for 59.
Pakistan slipped to 191 for nine after fast bowler Kallis had Shoaib Akhtar caught by Boucher for four and medium pacer Pollock had Danish Kaneria caught by Herschelle Gibbs in the gully for one.
But South Africa's progress was held up by Pakistan captain Inzamam, who hit 13 fours in his unbeaten 92 and shared a 10th-wicket partnership of 74 with Mohammad Asif (7).
South Africa squandered a difficult chance to dismiss Inzamam for 35 with the total on 195 for nine when the Pakistani edged a pull shot off Kallis and Boucher leapt high but failed to hold the catch.
'BIG ROLE'
"Inzamam played a big role today," Ntini said. "We opened the field for him and invited him to run, but he never did. He was happy to stand at one end for four balls, and then take a single."
South Africa stumbled to 18 for one in the fifth over before tea when Graeme Smith (10) edged a delivery from fast bowler Asif to first slip for Inzamam to take a diving catch.
Asif struck again to bowl AB de Villiers for 15 and Sami uprooted Hashim Amla's middle stump for 16. However, Kallis and Prince steadied the innings with a stand of 54 for the unbroken fourth wicket.
Pakistan fast bowler Shoaib Akhtar did not take the field in South Africa's second innings because of a hamstring strain.
Pakistan's Imran Farhat was cleared of breaching the International Cricket Council's code of conduct for claiming a catch off Prince that television replays showed had bounced.
"The umpires got together and watched the replays of the incident, and decided that the fielder should have known the ball had bounced," match referee Chris Broad told a news conference.
"I felt that until they had seen the slow motion replay no-one had questioned whether the ball had bounced. There was no blame laid at the fielder's door."
South Africa won the first Test by seven wickets.
Scorecard
South Africa (1st innings): 124 (M.Boucher 35, G.Smith 28; Shoaib Akhtar 4-36)
Pakistan (1st innings): 265 (Inzamam-ul-Haq 92, Younis Khan 45; M.Ntini 6-59)
South Africa (2nd innings):
G Smith c Inzamam-ul-Haq b Mohammad Asif 10
A de Villiers b Mohammad Asif 15
H Amla b Mohammad Sami 16
J Kallis not out 50
A Prince not out 21
Extras: (nb-3) 3
Total: (for 3 wkts, 52 overs) 115
Fall of wickets: 1-18, 2-30, 3-61.
To bat: M Boucher, S Pollock, P Harris, A Nel, M Ntini.
Bowling: Asif 16-6-32-2, Sami 12-4-31-1 (nb-3), Danish Kaneria 19-6-35-0, Imran Farhat 5-0-17-0.
