Santiago Cordero, who moved from Exeter Chiefs to Bordeaux-Begles during the off season, comes in at right wing in place of Matias Moroni, who moves to outside center as Matias Orlando drops to the bench.
The final change sees Joaquín Tuculet picked at full-back ahead of Emiliano Boffelli.
After naming 13 players from Super Rugby runners-up Jaguares against the All Blacks, Ledesma has picked four foreign-based players to face the Wallabies.
Stade Francais fly-half Nicolás Sánchezz and Saracens prop Juan Figallo keep their places.
Two more players, blindside flanker and captain Pablo Matera and lock Tomás Lavanini, played for Jaguares in their 19-3 defeat to the Canterbury Crusaders earlier this month but will join Stade Francais and Leicester Tigers respectively next season.
Australia began their campaign with a 35-17 defeat away to South Africa.
Joaquín Tuculet; Santiago Cordero, Matías Moroni, Jerónimo de la Fuente, Ramiro Moyano; Nicolás Sánchez, Tomás Cubelli; Facundo Isa, Tomás Lezana, Pablo Matera (capt); Tomás Lavanini, Guido Petti; Juan Figallo, Julian Montoya, Nahuel Tetaz Chaparro
Replacements: Santiago Socino, Mayco Vivas, Ramiro Herrera, Matías Alemanno, Juan Manuel Leguizamon, Felipe Ezcurra, Joaquín Diaz Bonilla, Matías Orlando