Captain Babar and Mohammad Rizwan (73 not out) combined in a remarkable opening stand of 197 off 17.4 overs, making light work of an imposing total posted by the Proteas, similarly thanks to 108 compiled at the top of the order by Janneman Malan and Aiden Markram, who scored 55 and 63 respectively.
Both openers fell to Mohammad Nawaz (2-38) – crucial blows before Babar and Rizwan took centre stage to give Pakistan a 2-1 lead in the four-match series.
Earlier on Wednesday, Babar usurped Virat Kohli at the top of the ODI batting rankings and he celebrated with his maiden ton in the shorted international format.
He reached the landmark off 49 deliveries, with Rizwan playing a relative anchor role, even though his 47-ball knock also progressed at a rapid rate
Babar just failed to see things through, caught behind when trying to ramp a bouncer outside off stump from Lizaad Williams (1-34), but Fakhar Zaman underscored Pakistan's dominance by hitting the next two deliveries for four to seal victory with two overs to spare.
It seemed utterly improbable to imagine South Africa being on the wrong side of such an emphatic result when Malan and Markram got to work.
Markram now has three successive T20I half-centuries, while Malan reached his 50 for the first time in the format.
However, after he spooned Nawaz to short third man with the score 143-3 after 14.1 overs, South Africa struggled to regain momentum, even though brisk knocks from George Linde (22) and Rassie van der Dussen (34 not out) looked to have given them plenty to defend. Babar and Rizwan had other ideas.
Babar brilliance to the fore once more
A century in the first ODI and a 94 in the third helped Babar to overhaul Kohli and he continued to make hay. Over the course of a mesmerising 59-ball stay, he hammered 15 fours and four sixes as he and Rizwan bent the Proteas attack to their will.
No tonic for Hendricks
It was hard going for all of South Africa's bowlers but left-arm seamer Beuran Hendricks will want to forget this one in a hurry. He sent down four overs at the cost of 55, without reward. Hendricks bowled three dot balls and was smoked for as many sixes.
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