Halfback Craig Casey has also been handed his maiden Six Nations start for the Irish in Saturday's clash in Rome.
Sexton is still recovering from the groin injury he suffered in the big win over France two weeks ago, but was still intending to travel with the team on Thursday.
Casey is in for Conor Murray, who has a place on the bench.
They were among seven changes to Ireland's team on Thursday after their victory over defending champions France 32-19 in Dublin.
Hooker Ronan Kelleher replaces Rob Herring, who suffered a head injury in an illegal tackle by France prop Uini Atonio.
Iain Henderson is in the second row with interim captain James Ryan after Tadhg Beirne was ruled out for up to three months by an ankle injury.
Jack Conan was starting at No.8, moving Caelan Doris to the blindside flank. Peter O'Mahony was on the bench.
The other change to the backline features Bundee Aki displacing Stuart McCloskey after playing the last two Tests off the bench.
Hooker Dan Sheehan, lock Ryan Baird and flyhalf Jack Crowley have come into the reserves.
Italy welcome back Paolo Garbisi for the game after the No.10 missed the first two rounds.
Garbisi injured right knee ligaments in action for Montpellier, and returned for the French Top 14 club off the bench last Saturday for half an hour.
That was enough for Italy coach Kieran Crowley to bring him back in. Garbisi and halfback Stephen Varney pair for the first time since the win over Samoa last November.
Tommaso Allan, who started in the last three Tests against South Africa, France and England — all losses — is in the reserves, among four changes.
Tommaso Menoncello, recalled for the England game two weeks ago, has been shifted from the left wing to inside centre at the expense of Luca Morisi.
Pierre Bruno has taken the vacant wing spot.
The only change in the pack is at tighthead, where Simone Ferrari and Marco Riccioni have swapped in and out again.
Italy: Ange Capuozzo, Edoardo Padovani, Juan Ignacio Brex, Tommaso Menoncello, Pierre Bruno, Paolo Garbisi, Stephen Varney; Lorenzo Cannone, Michele Lamaro (captain), Sebastian Negri, Federico Ruzza, Niccolo Cannone, Simone Ferrari, Giacomo Nicotera, Danilo Fischetti. Reserves: Luca Bigi, Federico Zani, Marco Riccioni, Edoardo Iachizzi, Giovanni Pettinelli, Alessandro Fusco, Luca Morisi, Tommaso Allan.
Ireland: Hugo Keenan, Mack Hansen, Garry Ringrose, Bundee Aki, James Lowe, Ross Byrne, Craig Casey; Jack Conan, Josh van der Flier, Caelan Doris, James Ryan (captain), Iain Henderson, Finley Bealham, Ronan Kelleher, Andrew Porter. Reserves: Dan Sheehan, Dave Kilcoyne, Tom O'Toole, Ryan Baird, Peter O'Mahony, Conor Murray, Jack Crowley, Stuart McCloskey.
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