The British Lion will make his first Test match appearance since the World Cup, as one of two changes coach Eddie O'Sullivan has made two changes following that 35-17 reversal.
O'Sullivan has dropped Bath centre Kevin Maggs and Leinster lock Malcolm O'Kelly, who boast 119 caps between them.
Maggs makes way for O'Driscoll, who will form an all-Leinster midfield combination alongside Gordon D'Arcy.
Munster lock Donncha O'Callaghan replaces O'Kelly.
It will be 24-year-old O'Callaghan's first Test start after winning all eight of his previous caps off the bench. He teams up with Munster second-row colleague Paul O'Connell.
Maggs and O'Kelly drop down to replacement duty, and there is no place in the 22 for Munster wing Anthony Horgan, who went on as a second-half substitute in Paris.
Ireland are bidding for a fifth successive victory over Wales.
Ireland team to play Wales in the RBS 6 Nations Championship at Lansdowne Road, Dublin: G Dempsey (Leinster); S Horgan (Leinster), G D'Arcy (Leinster), B O'Driscoll (Leinster, capt), T Howe (Ulster); R O'Gara (Munster), P Stringer (Munster); R Corrigan (Leinster), S Byrne (Leinster), J Hayes (Munster), D O'Callaghan (Munster), P O'Connell (Munster), S Easterby (Llanelli Scarlets), K Gleeson (Leinster), A Foley (Munster).
Replacements: F Sheahan (Munster), S Best (Ulster), M O'Kelly (Leinster), V Costello (Leinster), G Easterby (Rotherham), D Humphreys (Ulster), K Maggs (Bath).