Towering Pakistan seam bowler Mohammad Irfan took two wickets with the first two balls of the match as South Africa struggled to 234-9 in 50 overs in the fourth one-day international on Thursday.
Irfan removed Hashim Amla and then Colin Ingram for first-ball ducks to leave South Africa on 0-2 after two deliveries at Kingsmead. AB de Villiers (75) and David Miller (67) shared a century stand to lift the home team.
But Irfan, Junaid Khan and spinner Saeed Ajmal struck regularly taking three wickets each to keep the Proteas to a low score in a game the Pakistanis must win to keep the series alive.
The 2.16-metre (7-foot-1) Irfan finished with 3-46 as South Africa lost 5-81 when the De Villiers-Miller stand was broken.
South Africa 234 for 9 (de Villiers 75, Ajmal 3-42)