South Africa were all out for their lowest-ever total in T20 cricket, scoring only 74 as India won the series opener by 101 runs on Tuesday.
Hardik Pandya smashed an unbeaten 59 off 28 balls and India scored 175-6 after losing the toss.
South Africa never got their chase off the ground and collapsed from 45-3 to 74 all out in 12.3 overs with India's six bowlers getting at least a wicket each.
South Africa's previous lowest T20 total of 87 was also against India, in 2022.
India had lost openers Abhishek Sharma (17) and Shubman Gill (4) cheaply before Pandya helped to revive the hosts from 78-4 in the 12th over. The all-rounder hit four sixes and six fours.
The five-match series is in preparation for the T20 World Cup in India in February.
India won the ODI series against South Africa 2-1 after losing the Test series 2-0 .
"I had to back my shots. I realised the wicket had a bit of spice. I had to be a bit gutsy," Pandya said after he was named player of the match.
"It was more about timing the ball, not breaking the ball. I was very satisfied with the way I was batting."
