De Kock, who opened the innings alongside Reeza Hendricks, scored 90 runs off 46 balls, his highest score against India in the format, helping his side to post a huge total of 213-4 in 20 overs in Chandigarh.
In response, Tilak Varma, who walked in at 32-3, struck a 27-ball fifty, but the left-handed batter was unable to take his side over the line.
"When I do get going, I try and make it count," De Kock said after he was named player of the match.
"The wicket was slow up front. Any new batter would find it harder."
After being asked to bat, South Africa's openers scored 38 runs in the first four overs, before leg-spinner Varun Chakravarthy broke the partnership with a quick googly, knocking down Hendricks's stumps.
De Kock continued the onslaught, scoring fifty in 26 balls with a flick off Hardik Pandya through midwicket for a four. An under-pressure Arshdeep Singh gave away seven wides in an over as South Africa built up momentum with an 83-run partnership between De Kock and Aiden Markram.
De Kock, who struck five fours and seven sixes, missed out on his century after a smart run out by wicketkeeper Jitesh Sharma ended his stay.
David Miller and Donovan Ferreira continued the fireworks in the death overs and, with India restricted to four fielders in deep in the final over as a penalty for maintaining a slow over-rate, the duo smashed Jasprit Bumrah for 18 runs to set a target of 214.
In the chase, India lost Shubman Gill for a golden duck, while Marco Jansen got rid of Abhishek Sharma and India skipper Suryakumar Yadav, before Baartman broke the 35-run stand between Axar Patel and Varma.
The Proteas kept danger man Hardik Pandya contained by not allowing him much room to play his shots, and, with the required rate climbing, the all-rounder gave away an easy catch in the deep to Brevis.
Varma's 34-ball 62 was not enough to turn the tide as Baartman picked up three more wickets in the 19th over, and his resistance was ended by pacer Lungi Ngidi as South Africa bowled out India for 162 in 19.1 overs to level the series 1-1.
The two teams will play the third game in the series on Sunday in Dharamsala.