Into the starting line-up come full-back Lucas Gonzalez Amorosino, left-wing Horacio Agulla, prop Marcos Ayerza and locks Julio Farias Cabello and Mariano Galarza.
Out go injured Los Pumas trio, full-back Juan Martin Hernandez and locks Manuel Carizza and Patricio Albacete.
Wing Juan Imhoff and prop Matias Diaz have been dropped to the bench from the side routed 73-13 in Soweto last Saturday.
Inspirational No. 8 and captain Juan Martin Fernandez Lobbe remains sidelined due to injury and was sorely missed against the Springboks.
His continued absence means centre Felipe Contepomi, who turns 36 this week, continues as skipper.
Argentina are returning to western city Mendoza hoping to recapture the form of last season when they were unlucky to only draw 16-16 against South Africa.
The Springboks won seven other Tests in Argentina since being readmitted to international rugby in 1992 after apartheid-induced isolation.
The biggest winning margin for the green and gold came from a 39-7 triumph in capital city Buenos Aires nine years ago.
15. Lucas Gonzalez Amorosino, 14. Gonzalo Camacho, 13. Marcelo Bosch, 12. Felipe Contepomi (captain), 11. Horacio Agulla, 10. Nicolas Sanchez, 9. Martn Landajo, 8. Leonardo Senatore, 7. Juan Manuel Leguizamon, 6. Pablo Matera, 5. Mariano Galarza, 4. Julio Faras Cabello, 3. Juan Figallo, 2. Eusebio Guinazu, 1. Marcos Ayerza
Substitutes: 16. Agustn Creevy, 17. Nahuel Lobo, Matas Diaz, 18. Tomas Lavaninni, 19. Benjamin Macome, 20. Tomas Cubelli, 21. Santiago Fernandez, 22. Juan Imhoff