The visitors were sent into bat and amassed 194 for nine in their 20 overs, before restricting Pakistan to 139 all out in reply.
Hendricks and fellow opener Quinton de Kock (23 from 13 balls) got their side off to a fast start, before debutant in this format, Tony de Zorzi, added a quickfire 33 from 16 deliveries and all-rounder George Linde 36 from 22.
Left-arm spinner Mohammad Nawaz was excellent with the ball for Pakistan and returned figures of 3-26 in four overs.
Pakistan were restricted by the South African seamers in their reply and never managed to build momentum in the innings, despite 37 from 28 balls at the top of the order from Saim Ayub.
Babar Azam, playing his first T20 international since December last year, did not last long as he spooned a catch to Hendricks at cover off Bosch for a two-ball duck.
South Africa spinner Linde was expensive early on but finished with 3-31.
"It was a collective effort. We had a good powerplay batting effort and Linde finished it well," South Africa captain Donovan Ferreira said. "We wanted to keep it nice and simple with the ball - top of off.
"We bowled well but we put up a good score too. Reeza held it together nicely for us which allowed George license to explode.
"(Bosch) had really good energy on the ball. He usually goes for the yorkers but he hit the deck today and got something out it. Four wickets is an amazing achievement."
The second match in the three-game series will be played in Lahore on Friday, before it concludes at the same venue on Saturday.