Sean Cronin has earned his first Six Nations start at hooker in place of Rory Best who is rested, while Dave Kilcoyne also starts in the front row.
Jordi Murphy is included in the back row and Ultan Dillane will make his Six Nations debut at lock, while Iain Henderson and uncapped fly-half Jack Carty are among the replacements.
Cronin, 32, has 68 caps to his name but 58 of those have come from the bench and none of his starts have been in the Six Nations.
Best misses just his second Six Nations match in the last 63, a run stretching all the way back to 2007, with Peter O'Mahony taking over as captain in his absence.
Carty could make his debut from the bench after he was drafted in for Joey Carberry who has a hamstring injury.
Italy have made five changes to their Starting XV for the match in Rome.
The most significant is in the back row where Braam Steyn shifts to No. 8 in place of captain Sergio Parisse, who is out with concussion.
Maxime Mbanda steps in as flanker and Jimmy Tuivaiti is also in the back row as he replaces Sebastian Negri, who has failed to overcome illness.
Elsewhere in the forwards Leonardo Ghiraldini is named as captain in Parisse's absence, Federico Ruzza comes in at lock after impressing from the bench and Andrea Lovotti is preferred at tighthead prop.
Benetton No. 9 Tito Tabaldi returns in place of Guglielmo Palazzini at scrum-half, while Alessandro Zanni and Tomasso Castello are among the replacements.
Ireland sit fourth in the Six Nations table after an important 22-13 win over Scotland at Murrayfield in Round 2. Last year's Grand Slam winners were humbled by England in Dublin on the opening weekend, losing 32-20.
Italy return to Rome for the clash at the Stadio Olimpico two weeks after they lost 26-15 to Wales, leaving them bottom of the table. But there was encouragement in their performance and there were also good moments in their 33-20 defeat to Scotland at Murrayfield in Round 1.
Italy Starting XV: 15. Jayden Hayward, 14. Edoardo Padovani, 13. Michele Campagnaro, 12. Luca Morisi, 11. Angelo Esposito, 10. Tommaso Allan, 9. Tito Tebaldi; 1. Andrea Lovotti, 2-Leonardo Ghiraldini (captain), 3. Simone Ferrari, 4. Federico Ruzza, 5. Dean Budd, 6.Jimmy Tuivaiti, 7. Maxime Mbanda, 8. Braam Steyn
Replacements: 16. Luca Bigi, 17. Cherif Traore, 18. Tiziano Pasquali, 19. David Sisi, 20. Alessandro Zanni, 21. Guglielmo Palazzani, 22. Ian McKinley, 23. Tomasso Castello.
Ireland Starting XV: 15. Rob Kearney, 14. Keith Earls, 13. Chris Farrell, 12. Bundee Aki, 11. Jacob Stockdale, 10. Jonathan Sexton, 9. Conor Murray, 1. Dave Kilcoyne, 2. Sean Cronin, 3. Tadhg Furlong, 4. Ultan Dillane, 5. Quinn Roux, 6. Peter O'Mahony (captain), 7.Sean O'Brien, 8. Jordi Murphy,
Replacements: 16. Niall Scannell, 17. Jack McGrath, 18. John Ryan, 19. Iain Henderson, 20. Josh van der Flier, 21. John Cooney, 22. Jack Carty, 23. Andrew Conway