However, South Africa were bundled out on 124 with 19.1 overs to spare.
Dane van Niekerk, the captain who bowls legspin, was wicketless but held her own in a run-fest with figures of 10-1-38-0.
Apart from new-ball bowler Marizanne Kapp and legspinner Dane van Niekerk, every other South Africa bowler leaked more than six runs an over.
Troubled by the Indian wrist spinners, the Proteas have seemed a lost pack unable to solve the puzzle. Chahal took his maiden five-for in this format, bowling conventional leg spin.
The bowler was JP Duminy, who bowled his quota of overs for the fifth time in his 182 ODIs, and for the first time since 2013. If you defend a lot of balls it is of no use. If he can give South Africa a stable start and set up a solid base, the middle-order can be counted on to provide the flair for the home team to stay alive in the series. Unfortunately for him, Jasprit Bumrah came armed with a counter. Wrist-spinners Yuzvendra Chahal and Kuldeep Yadav have performed exceptionally well on the South African pitches causing maximum damage in both the matches. The Indian captain hit Kagiso Rabada for a six and a four off the last two balls of the innings to take India over 300. Kohli was doubtful but reviewed it, and was bailed out by the snickometer that showed a deviation in the wave when the ball went past the bat.
While the hosts didn't rename a replacement for de Kock, young keeper Heinrich Klaasen, who finished as the third highest run-getter in South Africa's domestic one-day tournament, is expected to make his ODI debut. Duminy, who bowled his allotted 10 overs on the trot from the Kelvin Grove End, followed up Dhawan's dismissal by trapping Ajinkya Rahane lbw for 11 and Chris Morris removed the unsafe Hardik Pandya for 14 to see India lose three wickets for 48 runs.
Earlier, put in to bat, India got off to a flier with Smriti and Poonam Raut (20, 37 balls, 4x3) putting on 56 runs, before Poonam departed caught behind by Trisha Chetty off pacer Marizanne. With MS Dhoni at the other end, he reached his century off 119 deliveries.
Kohli said India wanted to post a good total and then challenge an inexperienced South African batting line-up to chase a target.
In the company of Bhuvneshwar Kumar however, that was made possible as the tailender constantly turned over the strike and didn't try anything too expansive himself.
India look to take an unassailable lead in the third ODI.