O'Shea made just two changes on the bench with lock Federico Ruzza taking Marco Lazzaroni's place and Tito Tebaldi coming in for scrum-half Edoardo Gori.
Italy beat Fiji 19-10 in Catania last Saturday with Argentina losing their opening November Test 21-8 to England at Twickenham.
O'Shea said he wanted to build on the victory which ended a series of nine consecutive defeats going back to Italy's shock victory over South Africa in November 2016 in Florence.
"I know this is a difficult choice for the six players in the squad who have not yet had an opportunity in these November tests," said O'Shea.
"But after the Catania game we wanted consistency especially for a game such as the one against the Pumas that will be, in every respect, much more challenging and difficult to deal with."
Irishman O'Shea made his debut as Italy coach when the two sides last clashed in June 2016 in Santa Fe with the South Americans winning 30-24.
The Pumas have 15 wins, five losses and a draw in 21 meetings with the Italians, and are on a winning streak going back to the autumn of 2008 in Turin.
"Patience and precision will be the key to the match," O'Shea added.
Argentina coach Daniel Hourcade made four changes from the Twickenham defeat.
Among the forwards Juan Manuel Leguizamon replaces Tomas Lezana, while Nicolas Sanchez, Matias Orlando and Sebastian Cancelliere got the nod ahead of Juan Martin Hernandez, Matias Moroni and Ramiro Moyano.
Guido Petti Pagadizabal moves onto the bench after missing the cut against England.
Jayden Hayward, Leonardo Sarto, Tommaso Boni, Tommaso Castello, Mattia Bellini, Carlo Canna, Marcello Violi, Sergio Parisse (capt), Abraham Steyn, Francesco Minto, Dean Budd, Marco Fuser, Simone Ferrari, Luca Bigi, Andrea Lovotti
Leonardo Ghiraldini, Federico Zani, Dario Chistolini, Federico Ruzza, Giovanni Licata, Tito Tebaldi, Ian McKinley, Matteo Minozzi
Coach; Conor O'Shea (IRL)
Joaquin Tuculet; Sebastian Cancelliere, Matias Orlando, Santiago Gonzalez Iglesias, Emiliano Boffelli; Nicolas Sanchez, Martin Landajo, Juan Manuel Leguizamon, Marcos Kremer, Pablo Matera; Tomas Lavanini, Matias Alemanno; Nahuel Tetaz-Chaparro, Agustin Creevy (capt), Santiago Garcia-Botta
Replacements: Julian Montoya, Lucas Noguera, Enrique Pieretto, Guido Petti Pagadizabal, Benjamin Macome, Gonzalo Bertranou, Juan Martin Hernandez, Matias Moroni
Coach: Daniel Hourcade (ARG)