Quinton de Kock and Hashim Amla gave South Africa a flying start, putting on 72 for the first wicket before Amla was bowled by Pakistan captain and off-spinner Mohammad Hafeez for 31 off 20 balls.
De Kock made 43 off 33 deliveries before he was well caught at long-on by Sohail Tanvir off Hafeez.
A third wicket fell to slow bowling in the space of 15 runs when Shahid Afridi bowled Henry Davids for three.
The success of the slower men made it puzzling that Pakistan made a late switch in their team, leaving out their world-class off-spinner Saeed Ajmal at the last minute, causing a delay in the toss.
With play starting 25 minutes late following a thunderstorm, Hafeez said it was the first time he had seen the pitch. Ajmal was in the team list handed to the media before the toss but it transpired the change was made as a result of seeing a pitch expected to favour fast bowlers. Junaid Khan, not originally named, took the field instead of Ajmal after Hafeez sent South Africa in.
Hafeez and Afridi took three wickets between them for 39 in their combined eight overs as the South African innings lost momentum.
South Africa won both Twenty20 matches in the United Arab Emirates last week before both teams travelled to South Africa for a hastily-arranged reciprocal series. But Pakistan gained a convincing 95-run win when the teams last clashed in South Africa, in Centurion in March.