O Driscoll has recovered from a hamstring injury to replace Kevin Maggs at inside centre and earns his 47th cap in a new midfield partnership with Gordon D Arcy, who retains O Driscoll s traditional outside centre position.
In the second row, Donnacha O Callaghan, who has won all his eight previous caps as a replacement since making his debut in the corresponding game last year, is chosen to play for the first time in place of 60 times capped Malcolm O Kelly, who is now in the replacements.
The only other change in the replacements sees Kevin Maggs replace Anthony Horgan and if Maggs is called into the game he will earn his 60th cap.
The Ireland v Wales match will mark the 40th test appearance for out half Ronan O Gara.
The Ireland team to play Wales in the RBS Six Nations Championship in Lansdowne Road on Sunday 22nd February at 15.00hrs is as follows:
15 Girvan Dempsey (Leinster Terenure College) 14 Shane Horgan (Leinster Lansdowne) 13 Gordon D Arcy (Leinster Lansdowne) 12 Brian O Driscoll (Leinster - Blackrock College) Captain 11 Tyrone Howe (Ulster Dungannon) 10 Ronan O Gara (Munster Cork Constitution) 9 Peter Stringer (Munster Shannon) 1 Reggie Corrigan (Leinster Greystones) 2 Shane Byrne (Leinster Blackrock College) 3 John Hayes (Munster Shannon) 4 Donnacha O Callaghan (Munster Cork Constitution) 5 Paul O Connell (Munster Young Munster) 6 Simon Easterby (Llanelli) 7 Keith Gleeson (Leinster St. Mary s College) 8 Anthony Foley (Munster Shannon)
Replacements: 16 Frank Sheahan (Munster Cork Constitution), 17 Simon Best (Ulster Belfast Harlequins), 18 Malcolm O Kelly (Leinster St. Mary s College), 19 Victor Costello (Leinster St. Mary s College), 20 Guy Easterby (Rotherham), 21 David Humphreys (Ulster Dungannon), 22 Kevin Maggs (Bath)
Not considered due to injury:
Denis Hickie (Leinster - St. Mary s College), Marcus Horan (Munster Shannon), Eric Miller (Leinster Terenure College), Mike Mullins (Munster Old Crescent) Geordan Murphy (Leicester), Alan Quinlan (Munster Shannon), David Wallace (Munster Garryowen).