The result was built on a clinical all-round performance, with the hosts first dismantling India's batting line-up before captain Laura Wolvaardt and Sune Luus delivered a commanding opening stand to make light work of the chase.
After being sent in to bat, India looked well placed at 99/2, driven by a fluent 57 from Shafali Verma, who struck boundaries at will and cleared the ropes twice. However, a dramatic collapse followed as the visitors lost seven wickets for just 33 runs to be bowled out for 147.
Left-arm spinner Chloe Tryon was central to the turnaround, claiming 3/22 and removing key batters including Smriti Mandhana and Jemimah Rodrigues, both caught attempting sweep shots. Tumi Sekhukhune matched her impact with 3/31, while Nonkululeko Mlaba applied the squeeze with a miserly spell, conceding only 17 runs and dismissing Verma. A sharp run-out involving Annerie Dercksen and wicketkeeper Sinalo Jafta further dented India's resistance during the middle-order collapse.
Despite a late flourish that added 15 runs in the final over, India's total always appeared below par on a sluggish surface.
South Africa wasted little time asserting control in the chase. Wolvaardt and Luus dominated from the outset, racing to 66 without loss in the powerplay - equalling the team's best start in T20 internationals. Their partnership ultimately yielded 106 runs, effectively deciding the contest.
Wolvaardt led from the front with a polished 54, her second half-century of the series, striking boundaries with ease and accelerating confidently against both pace and spin. Luus complemented her skipper with a composed 57, growing into her innings after a measured start to keep the scoreboard ticking.
With South Africa cruising past 100 inside 11 overs, any hopes of an Indian comeback quickly faded. Both openers departed after reaching their fifties, but the foundation had already been laid.
Tazmin Brits and Annerie Dercksen calmly completed the chase, guiding the team home with 17 balls to spare and underlining the Proteas' superiority across all departments.
Having also won the opening match at the same venue, South Africa now head to Johannesburg for the third and fourth fixtures full of confidence, with the series concluding in Benoni.