Already Ireland's record goalscorer, the Dubliner will surpass Shay Given as their most capped player when he makes his 126th appearance.
Wes Hoolahan will make his first competitive start having impressed in the recent friendly success against Georgia.
The Norwich City playmaker replaces the suspended James McCarthy in central midfield as Ireland attempt to record their first home victory of the campaign against the bottom side in Group C.
Manager Giovanni Trapattoni has made wholesale changes to the side that thumped 10-man Georgia 4-0 last Sunday.
David Forde has been passed fit and starts in goal, but Richard Dunne must be content with a place on the bench as he continues his comeback from long-term injury.
John O'Shea and Sean St Ledger will renew their central defensive partnership, with the in-form Seamus Coleman and Marc Wilson occupying the full-back positions.
Glenn Whelan is named alongside Hoolahan in midfield, with Aiden McGeady on the left wing, while Simon Cox's reward for scoring against Georgia is a spot on the right flank.
Jonathan Walters will partner Keane in attack in a game they must win in order to stay in the hunt for World Cup qualification.
Ireland sit fourth in Group C, level on points with second-placed Austria and Sweden but with a much inferior goal difference.
Republic of Ireland: Forde, Coleman, O'Shea, St Ledger, Wilson, Cox, Whelan, Hoolahan, McGeady, Walters, Keane (c).