Debutant Nauman Ali finished with 5-35 and Yasir Shah took 4-79 as South Africa slumped to 245 all out in their second innings on the fourth day on a wearing National Stadium pitch that favoured spin bowlers.
Pakistan, needing 88 for victory, lost openers Abid Ali, Imran Butt and Babar Azam for a total of 52 runs before achieving the target in 22.5 overs to take a 1-0 lead in the two-match series.
The second Test starts on February 4 in Rawalpindi.
Azhar Ali was 31 not out while Fawad Alam -- who hit a fighting hundred in the first innings -- hit the winning boundary.
It was only Pakistan’s fifth victory against South Africa in 27 Tests.
Anrich Nortje bowled Abid in the first over after lunch and then had Butt caught behind to finish with figures of 2-24.
Azam, on his Test captaincy debut, was dismissed leg before by Keshav Maharaj.
It was a spinners’ battle on a brownish wicket, allowing Nauman to record figures of 7-73 and Yasir 7-133. In contrast, South Africa’s spinners managed just four wickets.
Pakistan had taken a crucial 158-run first innings lead, thanks to a fighting century from Fawad and half centuries from Faheem Ashraf and Azhar.
The writing was on the wall as South Africa lost nightwatchman Maharaj on the first ball of the day, bowled for two by pacer Hasan Ali.
South African skipper Quinton de Kock had a miserable 50th Test as he followed his 15 in the first innings with just two runs as he was caught off a lazy push off Yasir.
Temba Bavuma, who scored 40, added 42 for the seventh wicket with George Linde before being the last man out as Nauman took the last four wickets in a rapid 22 balls.
He dismissed Linde for 11, Kagiso Rabada for a single run, and Anrich Nortje for a duck, before removing Bavuma, to become the 12th Pakistani bowler to take five wickets in an innings on his debut.
South Africa are on their first tour of Pakistan for 14 years.
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