Pakistan dismissed South Africa for 195 to win the opening one-day international by 23 runs at Newlands in Cape Town.
After the tourists were restricted to 218-9 in their 50 overs, the Proteas were bowled out in 48.1 overs as debutant Bilawal Bhatti picked up three victims including the final wicket of Morne Morkel.
After winning the toss and electing to bat, Nasir Jamshed and Ahmed Shehzad gave Pakistan a steady start before Dale Steyn took wickets in consecutive overs.
When Steyn removed Shahid Afridi after a typically bright and breezy 26, the tourists were in real trouble at 131 for seven with 14 overs remaining.
However, debutants Bhatti (39) and Anwar Ali (43 not out) put on 74 for the eighth wicket to take Pakistan to a score they could defend.
It was the two novice seamers, 25-year-old Ali and 23-year-old Bhatti, who did the bulk of the damage with the ball.
Ali picked up the key wicket of Jacques Kallis for 50 to leave the hosts at 115-5 in the 26th over before removing David Miller.
A superb catch removed Vernon Philander, and then, Saeed Ajmal had JP Duminy caught behind for 49 in the 44th over. That left South Africa needing 51 from 41 balls.
However, Bhatti took the final two wickets as he got one to nip back and clean-bowl Steyn before yorking Morkel in the penultimate over.
The three-match series continues in Port Elizabeth on Wednesday before concluding at Centurion on Saturday.
South Africa won a recent five-match series between the sides in the United Arab Emirates 4-1.