Head coach Declan Kidney brings back Lions full back Rob Kearney in place of Geordan Murphy and Eoin Reddan starts ahead of Connor Murray in the second change to the backline.
Up front, there is a first World Cup appearance for Sean O'Brien, with Leinster's star flanker joining 2009 Lions Stephen Ferris and Jamie Heaslip in the back row. Cian Healy completes the changes having recovered from an eye injury, with the 23-year-old replacing Australian-born Tom Court at loosehead prop.
Ireland include nine Lions in their starting XV, with the same number of players coming from Heineken Cup holders Leinster.
Jonathan Sexton continues at fly-half ahead of Lions veteran Rona O'Gara despite a poor showing with the boot in Round 1, while Keith Earls again sees off the challenge of Andrew Trimble for a wing berth.
Lions Test star Tommy Bowe is the only man to play his rugby outside of Ireland, with the Ospreys wing joining Earls as one of the two non-Leinstermen to start among the backs.
Brian O'Driscoll will win his 115th Irish cap, taking his international total to 121 after six appearances for the Lions as he continues to close the gap on George Gregan's table-topping tally of 139.
O'Driscoll and midfield colleague Gordon D'Arcy will break the world record for appearances together as a centre partnership, with the Lions and Leinster duo set to surpass the 44-match tally they currently share with England's Will Carling and Jerry Guscott.
Ireland (vs Australia, Auckland, Saturday, 9.30am BST)
Rob Kearney (Leinster); Tommy Bowe (Ospreys),Brian O'Driscoll (captain) (Leinster), Gordon D'Arcy (Leinster), Keith Earls (Munster), Jonathan Sexton (Leinster), Eoin Reddan (Leinster); Cian Healy (Leinster), Rory Best (Ulster), Mike Ross (Leinster), Donncha O'Callaghan (Munster), Paul O'Connell (Munster), Stephen Ferris (Ulster), Sean O'Brien (Leinster),Jamie Heaslip (Leinster)
Replacements: Jerry Flannery (Munster), Tom Court (Ulster), Donnacha Ryan (Munster), Denis Leamy (Munster), Conor Murray (Munster), Ronan O'Gara (Munster), Andrew Trimble (Ulster)
NB bold denotes Lion