Pakistan batted out their 20 overs but could only make 98 for nine with Dale Steyn (three for 15), Lonwabo Tsotsobe (two for nine) and Imran Tahir (two for 17) doing most of the damage for the Proteas.
That target proved no problem whatsoever for South Africa as they knocked off the runs inside 15 overs for the loss of only Hashim Amla for 13.
Quinton de Kock finished unbeaten on 48 off 38 balls, which included two sixes and three fours, while captain Faf du Plessis contributed a 40-ball 37 not out to an unbroken second-wicket stand worth 83.
That partnership dwarfed the best effort of 29 that Pakistan managed in their innings as Mohammad Hafeez's men had a day to forget with the bat at the Dubai International Cricket Stadium.
Pakistan came into the match looking to bounce back from their 4-1 loss in the one-day international series against South Africa but they could barely have had a worse start with Ahmed Shehzad falling for a duck to the fifth ball of the innings from Tsotsobe.
Sohaib Maqsood (four) and Hafeez (nought) were then dismissed in the same Steyn over as Pakistan, who won the toss and opted to bat first, found themselves three down with only four runs on the board.
And the procession of wickets continued with only Umar Akmal, who made 49 off 41 balls before he was run out off the penultimate delivery, taking the fight to the five-pronged Proteas attack.
After the Pakistan wicketkeeper's score, the next-best tally was Shoaib Malik with 12.
South Africa wasted little time in claiming the victory, with De Kock and Du Plessis leading them home after star man Amla had been bowled by Sohail Tanvir in the third over.
The second of the two-match series takes place on Friday.