Kearney misses out because of a hamstring injury, with Zebo coming in at full-back for his second start of the tournament.
Zebo's inclusion is one of two changes made by head coach Joe Schmidt, who is able to welcome centre Jared Payne back to the XV.
Payne missed Ireland's 21-10 defeat to England??at Twickenham with a hamstring complaint, but returns to??partner??Robbie Henshaw in the centres.
Stuart McCloskey drops out of the squad altogether, while scrum-half Kieran Marmion is named on the bench with Eoin Reddan, who has been struggling with a calf issue, unable to prove his fitness.
There is no place in the squad for back row Tommy O'Donnell, with Josh van der Flier set to to earn his second cap at openside flanker.
Lock Ultan Dillane will also hope to win his second cap from the bench as Ireland seek a first victory??of what has been a disappointing title defence.
Ireland are fifth in the table having drawn with Wales and been beaten by France and England.??
Ireland team to face Italy:??Simon Zebo, Andrew Trimble, Jared Payne, Robbie Henshaw, Keith Earls; Jonathan Sexton, Conor Murray; Jack McGrath, Rory Best (Captain), Mike Ross, Donnacha Ryan, Devin Toner, CJ Stander, Josh van der Flier, Jamie Heaslip.
Replacements: Sean Cronin, Cian Healy, Nathan White, Ultan Dillane, Rhys Ruddock, Kieran Marmion, Ian Madigan, Fergus McFadden.