Blindside flank Mohoje, who made his debut off the bench against Scotland in June, was preferred to the experienced Schalk Burger as a replacement for Francois Louw who misses out through injury.
Bok coach Heyneke Meyer says he is excited about 24-year-old Mohoje, known locally as 'Oupa', and believes this will be the start of a long international career.
"Oupa will be a great Springbok, he has all the attributes and he has been training hard and giving a lot," Meyer told reporters on Wednesday. "He is good in the line-outs and a good ball-carrier. I have a good feeling about him, I think he will have a great game."
Meyer said he chose the rookie over Burger as he had been part of the travelling squad to Australia and New Zealand while the 2007 World Cup winner has only recently returned to the team after a stint in Japan.
"Schalk has only been with us for a few days, so it was better for our continuity," Meyer said.
Francois Hougaard comes in for injured scrumhalf Ruan Pienaar, while there are also four changes on the bench, including a place for uncapped scrumhalf Cobus Reinach.
Other new names among the replacements are Burger, lock Bakkies Botha and wing JP Pietersen.
It will be Hougaard’s first start for the Springboks since the final Test in 2012, against England at Twickenham.
"Francois brings different strengths to the team at number nine and has an opportunity to demonstrate the contribution he can make on Saturday," Meyer said.
"We felt we needed a couple of cool and experienced heads late in our matches and that is where Bakkies, Schalk, JP, Pat Lambie and Bismarck du Plessis will play a vital role – all of them have more than 30 caps."
South Africa and Australia have 10 points after four rounds of the Rugby Championship and trail leaders New Zealand by six.
The All Blacks will claim the title if they win with a bonus point against Argentina in La Plata on Saturday, although they may not need the extra point if neither South Africa nor Australia take five from their game in Cape Town.
Team:
15-Willie le Roux; 14-Cornal Hendricks, 13-Jan Serfontein, 12-Jean de Villiers (captain), 11-Bryan Habana, 10-Handre Pollard, 9-Francois Hougaard, 8-Duane Vermeulen, 7-Teboho Mohoje, 6-Marcell Coetzee, 5-Victor Matfield, 4-Eben Etzebeth, 3-Jannie du Plessis, 2-Adriaan Strauss, 1-Tendai Mtawarira.
Replacements: 16-Bismarck du Plessis, 17-Trevor Nyakane, 18-Marcel van der Merwe, 19-Bakkies Botha, 20-Schalk Burger, 21-Cobus Reinach, 22-Pat Lambie, 23-JP Pietersen.
(Editing by Amlan Chakraborty)
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