The tourists lost both openers early on a bouncy wicket. The first to go was Fakhar Zaman (1), followed by Imam-ul-Haq (8). Azhar Ali could not stay on for much longer either, and departed for 2, leaving the team at 19-3.
South Africa won the first Test in Pretoria by six wickets inside eight sessions as both bowling attacks found conditions to their liking with seam movement, and at times steep bounce.
Pakistan are bolstered by the return of pacer Mohammad Abbas, who missed the first Test with a shoulder injury.
He has made a remarkable start to his Test career with 61 wickets in 12 matches at an average of 16.62.
Seamer Vernon Philander is also back for South Africa.
South Africa have won all three previous Tests against Pakistan at Newlands and have only lost four times in 24 matches against the sub-continent side at all venues.
Imam-ul-Haq, Fakhar Zaman, Shan Masood, Azhar Ali, Asad Shafiq, Babar Azam, Sarfraz Ahmed (capt/wk), Mohammad Amir, Yasir Shah, Shaheen Afridi, Mohammad Abbas
Dean Elgar, Aiden Markram, Hashim Amla, Theunis de Bruyn, Faf du Plessis (capt), Temba Bavuma, Quinton de Kock (wk), Vernon Philander, Kagiso Rabada, Dale Steyn, Duanne Olivier