Heading into the match, the Men in Blue have suffered a big blow as they will be without their star captain Virat Kohli, who is suffering from a stiff back.
Jaspreet Bumrah and Axar Patel have been called up in place of Jaydev Unadkat and Yuzvendra Chahal, respectively.
Having won the five-match ODI series already, India will aim to return home with two trophies.
The three-match T20I series is currently tied at 1-1. India won the first game by 28 runs in Johannesburg, but tasted six-wicket defeat in the second after extraordinary innings from Henrich Klaasen and JP Duminy.
South Africa, on the other hand, have lost five of the eight games played at the venue.
The two squads are as follows:
South Africa Playing XI: David Miller, Reeza Hendricks, JP Duminy (capt), Heinrich Klaasen (wk), Farhaan Berhadien, Christiaan Jonker, Chris Morris, Andile Phehlukwayo, Aaron Phangiso, Junior Dala, Tabraiz Shamsi. (ANI)