Senatore is named at Number Eight, with Juan Martin Fernandez Lobbe missing with a calf injury, while fellow Warriors new boy and hooker Agustin Creevy is among the replacements.
Senatore is one of eight changes from the team beaten 27-6 by the Springboks in Cape Town at the same stage last year. Senatore and flankers Pablo Matera and Juan Manuel Leguizamon form a fresh back row in place of Lobbe, Alvaro Galindo and Julio Farias Cabello.
The Rugby Championship was expanded last season to include Argentina, which proved competitive apart from a 54-15 home defeat from world champions, New Zealand.
Los Pumas prepared for Soweto by defeating the visiting New South Wales Barbarians 29-27 and 58-12 in a two-match series.
Argentina:Juan Martin Hernandez; Gonzalo Camacho, Marcelo Bosch, Felipe Contepomi (captain), Juan Imhoff; Nicolas Sanchez, Martin Landajo; Leonardo Senatore, Juan Martin Leguizamon, Pablo Matera; Patricio Albacete, Manuel Carizza; Matias Diaz, Eusebio Guinazu, Juan Figallo
Replacements: Agustin Creevy, Nahuel Lobo, Juan Pablo Orlandi, Mariano Galarza, Julio Farias Cabello, Tomas Cubelli, Santiago Fernandez, Horacio Agulla