Back-row forward Juan Manuel Leguizamon will captain Argentina against England at Twickenham on Saturday in the absence of Juan Martin Fernandez Lobbe.
Fernandez Lobbe, 31, has been ruled out of the Pumas' three autumn Tests in Europe with a fractured elbow.
New coach Daniel Hourcade has made five changes from the team crushed 54-17 by Australia in the Rugby Championship.
Full-back Lucas Gonzalez Amorosino, centre Santiago Fernandez and scrum-half Tomas Cubelli come into the side.
Amorosino replaces the injured Juan Martin Hernandez, Fernandez takes over from the now-retired Felipe Contepomi, while Cubelli has been preferred to Martin Landajo, with both nines playing their club rugby in the amateur Buenos Aires championship.
Maximiliano Bustos comes into the front row for injured prop Juan Figallo, while a late change sees Eusebio Guinazu retain his place after Agustin Creevy withdrew injured.
Further positional changes see brilliant youngster Pablo Matera move from open-side flanker to blind-side to cover the absent Lobbe, while Julio Farias Cabello switches from lock to open-side.
Hourcade took charge last week following the resignation of Santiago Phelan, after Argentina went winless for a second year in the southern hemisphere Rugby Championship.
Former London Irish number eight Leguizamon, who has won 52 caps. will also lead Argentina against Wales and Italy this month.
"We face three very tough matches and we must work to the full each week to be able to go into them in the best shape," said 30-year-old Leguizamon, who now plays for French side Lyon.
Fernandez Lobbe fractured his right elbow during Toulon's Top 14 defeat against Toulouse. He will have an operation and is likely to be out of action for three months.
Meanwhile former Wales and New Zealand head coach Sir Graham Henry has left his role as technical advisor to the Pumas.
The World Cup-winning coach will not return after two years in the role and will concentrate solely on a similar role with Super Rugby side the Blues.
Argentina team: Lucas Gonzalez Amorosino, Horacio Agulla, Marcelo Bosch, Santiago Fernandez, Juan Imhoff, Nicolas Sanchez, Tomas Cubelli; Marcos Ayerza, Eusebio Guinazu, Maximiliano Bustos, Mariano Galarza, Patricio Albacete, Pablo Matera, Julio Farias Cabello, Juan Manuel Leguizamon (captain).
Replacements: Santiago Iglesias, Nahuel Lobo, Juan Pablo Orlandi, Manuel Carizza, Benjamín Macome, Martin Landajo, Gonzalo Tiesi, Santiago Cordero.