India, who suffered their first loss of the tour, were 240 all out following half centuries from Deepti Sharma (79) and Veda Krishnamurthy (56).
South Africa left-arm pacer Shabnim Ismail did the maximum damage with four wickets while conceding 30 runs in nine overs.
After opting to bat, India decided to send Sharma at the top in the absence of Poonam Raut. The visitors also rested veteran pacer Jhulan Goswami for the dead rubber.
India were dealt a big blow in the first over of the match when Ismail dismissed the in-form Smriti Mandhana (0).
Mandhana had made a match-winning 135 and 84 in the first two ODIs.
Deepti, on the other hand, grabbed the opportunity with both hands and was unfortunate to miss out on a hundred.
Deepti shared an 83-run stand with Veda for the fourth wicket, stabilising the innings after India lost three wickets for 57 runs in th 18th over.
After the opener's fall, du Preez got the job done with the support of captain Dane van Niekerk, who remained unbeaten on 41.
Both teams now switch to the shortest format with the five-match T20 series beginning here on February 13.
(This story has not been edited by Business Standard staff and is auto-generated from a syndicated feed.)