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.
Ulster’s Cave will take the number 13 shirt that belonged for so long to now-retired talisman Brian O’Driscoll.
Leinster pair Devin Toner and Jamie Heaslip drop to the bench after helping their province to the Celtic League 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.
Felix Jones; Andrew Trimble, Darren Cave, Luke Marshall, Simon Zebo; Jonathan Sexton, Conor Murray; Jordi Murphy, Chris Henry, Robbie Diack; Paul O’Connell (capt), Iain Henderson; Mike Ross, Rory Best, Jack McGrath
Replacements: Damien Varley, Dave Kilcoyne, Rodney Ah You, Devin Toner, Jamie Heaslip, Kieran Marmion, Ian Madigan, Fergus McFadden