The Republic skipper is struggling with an adductor muscle injury he picked up in Friday's win over Andorra.
Keane has been unable to train since the game and he will now be forced to sit out the crucial qualifier as the Republic look to secure at least a play-off place.
West Brom forward Simon Cox will replace Keane in the side, getting the nod ahead of Baggies team-mate Shane Long to partner Kevin Doyle in attack.
In the absence of Keane, Shay Given will captain the Republic at the Avvia Stadium.
The Irish welcome back Richard Dunne after suspension and he will return in place of Darren O'Dea, while Stephen Kelly will take the place of the banned Stephen Ward.
A point for the Republic would secure a place in the play-offs to qualify for next year's finals, but a win for Armenia would see them leapfrog Giovanni Trapattoni's men.
Kick-off is at 6.45pm.
Republic of Ireland team: Given, O'Shea, Dunne, St Ledger, S Kelly, McGeady, Whelan, Andrews, Duff, Doyle, Cox.