Murphy comes into the side in place of Girvan Dempsey and Flannery takes over from Rory Best in the front row.
Stephen Ferris returns to blindside flanker after starting in that position against Canada and coming on as a replacement last weekend against New Zealand.
In the forward replacements, Malcolm O'Kelly, who remains Ireland's most-capped player, is named as cover for second row.
One position has been left vacant and will be confirmed following the appeal of Alan Quinlan's three-week suspension. The appeal will be heard tomorrow (Friday).
There are still a limited number of tickets left for Saturday's game, due to late returns - click here.
IRELAND TEAM & REPLACEMENTS (v Argentina, GUINNESS Series 2008, Saturday, November 22, Croke Park, kick-off 2.45pm):
15 - Geordan Murphy (Leicester Tigers)
14 - Tommy Bowe (Ospreys)
13 - Brian O'Driscoll (UCD/Leinster) (capt)
12 - Luke Fitzgerald (Blackrock College/Leinster)
11 - Rob Kearney (UCD/Leinster)
10 - Ronan O'Gara (Cork Constitution/Munster)
9 - Tomas O'Leary (Dolphin/Munster)
1 - Marcus Horan (Shannon/Munster)
2 - Jerry Flannery (Shannon/Munster)
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 - Rory Best (Banbridge/Ulster)
17 - Tony Buckley (Shannon/Munster)
18 - Malcolm O'Kelly (St. Mary's College/Leinster)
19 - AN Other
20 - Eoin Reddan (London Wasps)
21 - Paddy Wallace (Ballymena/Ulster)
22 - Keith Earls (Young Munster/Munster)