South Africa won the toss and elected to bat but a collapse from a commanding position saw them post a below-par 143 all out in 37.5 overs.
That was never likely to challenge the home side and they reached their target with three wickets down and a huge 149 deliveries remaining.
South Africa made a good start to their innings with a 72-run opening stand between left-handers Quinton de Kock (53) and Lhuan-dre Pretorius (39), but lost their next nine wickets for the addition of only 71 runs.
Pakistan's spinners got the ball to grip off the surface, with Abrar Ahmed picking up career-best figures of 4-27. Salman Agha (2-18) and Mohammad Nawaz (2-31) were also excellent as they ripped through the middle order.
Abrar's first three wickets were all bowled as he bamboozled the South African batters with his variations.
"It has been teamwork and we have worked very hard across the formats so credit goes to the players," Pakistan captain Shaheen Shah Afridi said.
"We didn't get so much help in the first five-six overs but when the spinners came on, they made it tough."
Pakistan lost opener Fakhar Zaman for a second successive duck in the opening over but Saim anchored their innings to go with contributions from Babar Azam (27) and Mohammad Rizwan (32 not out).
"We did not score enough runs," South Africa stand-in captain Matthew Breetzke said.
"We were probably looking at 250. It was tough conditions and unfortunately we lost too many wickets there. Abrar bowled really nicely."
Pakistan begin a three-match ODI series against Sri Lanka on Tuesday, while South Africa stay on the sub-continent with the start of their two-match test series against India on Friday.
