The touring Proteas, who were without Graeme Smith because of concussion, won the toss and elected to bat first.
They lost opener Hashim Amla for just 10 runs, but Smith's replacement, Quinton de Kock, steadied their innings with a knock of 40 before he was stumped by Umar Akmal off the bowling of Shahid Afridi.
The same combination then accounted for Faf du Plessis, who had made 55 runs from 60 deliveries.
It was left to 29-year-old JP Duminy to record South Africa's highest score as he made 64 before he was caught by Mohammad Hafeez. The away side eventually lost eight wickets before they reached their 50-over limit. The series is currently level at one victory apiece.