Having played 93 times for Ireland and earned six Lions caps, Sunday's game will mark O'Driscoll's 100th Test match.
At half-back, Ronan O'Gara will earn his 93rd cap for Ireland and will be partnered by Tomas O'Leary.
Up front, young prop Cian Healy will pack down at loosehead alongside Jerry Flannery and John Hayes, making his first start in an Ireland senior jersey.
There are two other uncapped players in the squad with Sean Cronin named as replacement hooker and Jonathan Sexton as cover at out-half.
In all, there are two changes to the side that secured Ireland's first Grand Slam in 61 years against Wales last March, with Wallace and Healy coming in for Gordon D'Arcy and Marcus Horan.
IRELAND TEAM & REPLACEMENTS (v Australia, GUINNESS Series 2009, Croke Park, Sunday, November 15, kick-off 3pm):
15 - Rob Kearney (UCD/Leinster)
14 - Tommy Bowe (Ospreys)
13 - Brian O'Driscoll (UCD/Leinster) (capt)
12 - Paddy Wallace (Ballymena/Ulster)
11 - Luke Fitzgerald (Blackrock College/Leinster)
10 - Ronan O'Gara (Cork Constitution/Munster)
9 - Tomas O'Leary (Dolphin/Munster)
1 - Cian Healy (Clontarf/Leinster)*
3 - John Hayes (Bruff/Munster)
4 - Donncha O'Callaghan (Cork Constitution/Munster)
5 - Paul O'Connell (Young Munster/Munster)
6 - Stephen Ferris (Dungannon/Ulster)
7 - David Wallace (Garryowen/Munster)
8 - Jamie Heaslip (Naas/Leinster)
16 - Sean Cronin (Buccaneers/Connacht)*
17 - Tom Court (Malone/Ulster)
18 - Leo Cullen (Blackrock College/Leinster)
19 - Denis Leamy (Cork Constitution/Munster)
20 - Eoin Reddan (Lansdowne/Leinster)
21 - Jonathan Sexton (St. Mary's College/Leinster)*
22 - Keith Earls (Young Munster/Munster)
* Denotes uncapped player