Put into bat after India won the toss, the tourists built a commanding 213 for 4 thanks to a dominant top-order performance led by Quinton de Kock. The wicketkeeper-batter hammered 90 from just 46 balls, clearing the ropes seven times in an innings full of power and timing.
Captain Aiden Markram added 29 from 26 deliveries, while Dewald Brevis chipped in with 14 from 10.
The finishing touches came from Donovan Ferreira, who struck an unbeaten 30 off 16 balls, and David Miller, who ended on 20 not out from 12.
India also struggled with discipline, offering 16 wides as South Africa pushed beyond the 200 mark. Varun Chakaravarthy impressed with 2 for 29, and Axar Patel collected 1 for 27, but India's pace attack failed to contain the scoring.
India's chase faltered early and never recovered. Shubman Gill departed for a duck, Suryakumar Yadav managed only five, and Abhishek Sharma's 17 did little to settle the innings.
Tilak Varma provided resistance with a stylish 62 from 34 balls, striking cleanly through the off side, while Jitesh Sharma kept hopes alive briefly with 27 from 17. Hardik Pandya fought for 20 from 23, but regular wickets killed the momentum.
Ottneil Baartman led the Proteas attack superbly with 4 for 24, supported by Lungi Ngidi (2 for 26), Marco Jansen (2 for 25), and Lutho Sipamla (2 for 46).
India were dismissed for 162 in 19.1 overs, falling well short of the target and handing South Africa another commanding win early in the five-match contest.
Former Bafana Bafana striker Shaun Bartlett believes South Africa may finally have found a player capable of threatening the national team's long-standing goal-scoring records.
Hardik Pandya struck forceful half-century and then took a wicket as India crushed the Proteas by 101 runs in the first of five T20Is played in Cuttack on Tuesday.
Former Scotland head coach Matt Williams accused Eben Etzebeth of breaking rugby's social contract when he gouged the eye of Wales flank Alex Mann.
South Africa women cruised to a comfortable 65-run win in the second T20I against Ireland on the back of a strong performance from their batting lineup.
