Uncapped back-row forward Robbie Diack will make his Ireland debut against Argentina in Saturday's first Test in Resistancia.
South African-born Diack, 28, fills in for the injured Peter O'Mahony with fellow back-rower Jordi Murphy also poised to make his first Test start.
Simon Zebo, Jack McGrath, Iain Henderson, Felix Jones, Darren Cave and Luke Marshall were also drafted into the starting XV as coach Joe Schmidt made eight changes to the side that clinched the Six Nations title against France.
Cave, who plays for Ulster, will take the No 13 shirt that belonged for so long to now-retired talisman Brian O'Driscoll.
Leinster's Devin Toner and Jamie Heaslip drop to the bench after helping their province to the RaboDirect Pro12 title last weekend, while Cian Healy, Gordon d'Arcy, Sean O'Brien and Tommy Bowe have been all rested for the two-Test series.
Two other new faces in the squad are Connacht duo Kieran Marmion and Kiwi-born Rodney Ah You, who could make their debuts off the bench.
Schmidt said: "There are a number of players that are fatigued from the Pro12 final, there are a number of players that we wanted to give an opportunity. We have this one window to really do that.
“The Guinness series is going to be a immeasurably tougher with South Africa and Australia, but it’s going to be very, very tough here, and one of the things that you want to find out is how the players cope in a tough environment.
“It will be hostile, it’s a place where test match rugby hasn’t been before so the local population will be very much behind the Argentinians.”
Ireland: 15 Felix Jones (Munster), 14 Andrew Trimble (Ulster), 13 Darren Cave (Ulster), 12 Luke Marshall (Ulster), 11 Simon Zebo (Munster), 10 Jonathan Sexton (Racing Metro 92), 9 Conor Murray (Munster); 1 Jack McGrath (Leinster), 2 Rory Best (Ulster), 3 Mike Ross (Leinster), 4 Iain Henderson (Ulster), 5 Paul O'Connell (Munster, capt), 6 Robbie Diack (Ulster), 7 Chris Henry (Ulster), 8 Jordi Murphy (Leinster).
Replacements: 16 Damien Varley (Munster), 17 Dave Kilcoyne (Munster), 18 Rodney Ah You (Connacht), 19 Devin Toner (Leinster), 20 Jamie Heaslip (Leinster), 21 Kieran Marmion (Connacht), 22 Ian Madigan (Leinster), 23 Fergus McFadden (Leinster)
Argentina have named a largely experimental side with the bulk of the team coming from the second-string Pampas who won 2014 Pacific Rugby Cup - almost all of their players are based at home.
The exceptions include lock Manuel Carizza, who plays for Stormers in South Africa, and prop Matias Diaz of Highlanders in New Zealand.
Argentina: Joaquin Tuculet, Santiago Cordero, Jeronimo de la Fuente, Gabriel Ascarate, Manuel Montero, Nicolas Sanchez, Martin Landajo (capt); Lucas Noguera Paz, Matias Cortese, Ramiro Herrera, Manuel Carizza, Tomas Lavanini, Rodrigo Baez, Tomas de la Vega, Benjamin Macome.
Replacements: Julian Montoya, Bruno Postiglioni, Nahuel Tetaz Chaparro, Matias Alemanno, Javier Ortega Desio, Tomas Cubelli, Santiago Gonzalez Iglesias, Lucas Gonzalez Amorosino