Richardt Strauss will earn his first cap for Ireland at hooker in the front row alongside his Leinster colleagues Cian Healy and Mike Ross.
Mike McCarthy is selected in the second row alongside Donnacha Ryan, with Chris Henry lining out at openside flanker and Peter O'Mahony positioned at blindside.
Simon Zebo will be earning his first start for Ireland at full-back, in a back-three that has plenty of experience in Andrew Trimble and Tommy Bowe, who will be earning his 50th cap for Ireland since making his debut against the USA in 2004.
Jonathan Sexton and Conor Murray will combine at half-back once again with Gordon D'Arcy and Keith Earls completing the starting line-up as the centre partnership.
Among the replacements, forwards David Kilcoyne, Michael Bent and Iain Henderson are all in line to make their international debuts should they be called into the game.
IRELAND Team & Replacements (v South Africa, 2012 GUINNESS Series, Aviva Stadium, Saturday, November 10, kick-off 5.30pm):
15 - Simon Zebo (Cork Constitution/Munster/1 cap)
14 - Tommy Bowe (Belfast Harlequins/Ulster/49)
13 - Keith Earls (Young Munster/Munster/32)
12 - Gordon D'Arcy (Lansdowne/Leinster/69)
11 - Andrew Trimble (Ballymena/Ulster/48)
10 - Jonathan Sexton (St. Mary's College/Leinster/32)
9 - Conor Murray (Garryowen/Munster/12)
2 - Richardt Strauss (Old Wesley/Leinster) *
3 - Mike Ross (Clontarf/Leinster/22)
4 - Donnacha Ryan (Shannon/Munster/21)
5 - Mike McCarthy (Buccaneers/Connacht/4)
6 - Peter O'Mahony (Cork Constitution/Munster/7)
7 - Chris Henry (Malone/Ulster/2)
8 - Jamie Heaslip (Naas/Leinster/50) (capt)
16 - Sean Cronin (St. Mary's College/Leinster/21)
17 - David Kilcoyne (UL Bohemians/Munster) *
18 - Michael Bent (Leinster) *
19 - Donncha O'Callaghan (Cork Constitution/Munster/88)
20 - Iain Henderson (Ballynahinch/Ulster) *
21 - Eoin Reddan (Lansdowne/Leinster/45)
22 - Ronan O'Gara (Cork Constitution/Munster/124)
23 - Fergus McFadden (Old Belvedere/Leinster/14)
* Denotes uncapped player