The visiting team's wicketkeeper-batsman played the sheet-anchor's role to perfection in hot and sweltering conditions at the Saurashtra Cricket Association Stadium to make 103 in 118 balls after the visitors opted to bat first.
Courtesy De Kock's 9th hundred in his 50th ODI appearance along with Du Plessis' 63-ball-60, the visitors did well to set up a fighting target.
But the loss of three wickets just before the slog overs, including that of the centurion, arrested their progress though Farhan Behardien (33 off 36 balls) played a useful knock in the end.
De Kock was run out with the final 10 overs to come soon after du Plessis was dismissed and this was followed by the departure of their captain A B de Villiers, sent back by Axar Patel, off the next ball of the innings.
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The clutch of three quick wickets in the space of just 9 balls, left South Africa tottering at 210 for 5 with the last Powerplay just up.
Earlier, Indian spinners, Harbhajan Singh (1/41 in 10 overs) in particular, applied the brakes in time, after which the Proteas steadily built up the score before losing the three wickets in a hurry.
Choosing to bat first, South Africa were given a good start by their new all-leftie opening pair of Quinton de Kock and David Miller, promoted up the order after his twin failures earlier in the series, who put on 72 runs.
The scoring rate dropped significantly once Harbhajan, who bowled pretty impressively by varying his pace and had an extended opening spell of 1 for 31 in 8 overs.
With leg-spinner Amit Mishra (1/38 in 10 overs) brought on at the other end, and with the ball getting older the going became a little bit tougher for the South Africans after the brisk start that helped raise the 50 in the 9th over.