The outside centre position had been the main talking point ahead of the Irish team selection, with Tommy Bowe, Fergus McFadden, Andrew Trimble and Eoin O'Malley all having been mooted for the role.
"Keith is looking forward to it and has played well there for Munster," said Ireland head coach Declan Kidney.
"Players just want to play so they know they need to adapt. Keith's had a lot of time at 13 and is comfortable there."
Kidney has kept faith with the vast majority of the side that was beaten by Wales in the quarter-finals of last year's World Cup as he makes just three changes from that 22-10 reverse in Wellington.
Jonathan Sexton wins the battle for the fly-half role ahead of Lions veteran Ronan O'Gara, while Ulster's Andrew Trimble starts on the left wing as Earls moves into the midfield.
Connor Murray hangs on to the No9 shirt ahead of Eoin Reddan; double Lions tourist Gordon D'Arcy partners Earls in the centre and 2009 Test Lion Rob Kearney is named at full back.
The Irish pack is unchanged from its last outing, with Lions skipper Paul O'Connell leading the side in O'Driscoll's absence.
O'Connell's long-standing second row partner Donncha O'Callaghan keeps his place despite the fine form of Donnacha Ryan, while the front rows and back rows are as expected with Cian Healy, Rory Best, Mike Ross, Stephen Ferris, Sean O'Brien and Jamie Heaslip all looking for revenge against the Welsh.
Munster's Peter O'Mahony could make his debut from the bench despite only being called up to the senior squad earlier this week.
Ireland (v Wales, Aviva Stadium, Sunday, 3pm)
R Kearney; T Bowe, K Earls, G D'Arcy, A Trimble; J Sexton, C Murray; C Healy, R Best, M Ross; D O'Callaghan, P O'Connell; S Ferris, S O'Brien, J Heaslip
Replacements: S Cronin, T Court, D Ryan, P O'Mahony, E Reddan, R O'Gara, F McFadden
NB Bold denotes Lion