To see Rassie Erasmus' thoughts on the match, click here, or check out all the stats and facts.
The reshuffled front row are the only changes to the starting fifteen from the one that held holders New Zealand to a thrilling 16-16 draw in Wellington on 27 July. Duane Vermeulen will again lead the Springboks as captain for this decisive clash in the high altitude of Salta.
Mtawarira, the most experienced Springbok prop in history, and Nyakane replace Steven Kitshoff and Frans Malherbe, while Mbonambi takes over the hooker duties from Malcolm Marx.
All three front rankers who started the Test at the Westpac Stadium in the New Zealand capital are due to make an impact off the bench against the Pumas on Saturday.
The “Beast”, who is set to make his 110th appearance in the Green and Gold jersey, will join Rugby World Cup winner Bryan Habana on 53 appearances in the Castle Lager Rugby Championship to equal the Springbok record for number of caps in the southern hemisphere competition.
South Africa can clinch the Castle Lager Rugby Championship for the first time since 2009 if they can manage to beat the difficult Pumas with a bonus point. The Pumas picked a strong team for the Test - see it here.
The Springbok team for Salta (in order of name, franchise or club, caps and points):
15. Willie le Roux (Wasps, England), 54 caps, 60 points (12 tries)
14. Cheslin Kolbe (Toulouse, France), 8, 10 (2t)
13. Lukhanyo Am (Cell C Sharks), 7, 5 (1t)
12. Damian de Allende (DHL Stormers), 38, 20 (4t)
11. Makazole Mapimpi (Cell C Sharks), 6, 20 (4t)
10. Handré Pollard (Vodacom Bulls), 40, 350 (4t, 60c, 67p, 3d)
9. Faf de Klerk (Sale Sharks, England), 22, 15 (3t)
8. Duane Vermeulen (captain, Vodacom Bulls), 47, 15 (3t)
7. Pieter-Steph du Toit (DHL Stormers), 48, 20 (4t)
6. Kwagga Smith (Emirates Lions), 2, 0
5. Franco Mostert (Gloucester Rugby, England), 30, 5 (1t)
4. Eben Etzebeth (DHL Stormers), 77, 15 (3t)
3. Trevor Nyakane (Vodacom Bulls), 39, 5 (1t)
2. Bongi Mbonambi (DHL Stormers), 28, 15 (3t)
1. Tendai Mtawarira (Cell C Sharks), 109, 10 (2t)
16. Malcolm Marx (Emirates Lions), 25, 20 (4t)
17. Steven Kitshoff (DHL Stormers), 38, 5 (1t)
18. Frans Malherbe (DHL Stormers), 30, 0
19. RG Snyman (Vodacom Bulls), 13, 0
20. Francois Louw (Bath Rugby, England), 67, 45 (9t)
21. Herschel Jantjies (DHL Stormers), 2, 15 (3t)
22. Frans Steyn (Montpellier, France), 58, 132 (10t, 5c, 21p, 3d)
23. Jesse Kriel (Vodacom Bulls), 42, 60 (12t)