Craig Casey will partner Ross Byrne in a new half-back pairing for Grand Slam-chasing Ireland in Saturday's Six Nations contest against Italy in Rome.
Byrne's inclusion was expected with Johnny Sexton not risked after picking up a groin injury in the France game.
Like Byrne, scrum-half Casey is also handed a first Six Nations start as Conor Murray drops to the bench.
Bundee Aki replaces Stuart McCloskey at centre with Iain Henderson in for injured lock Tadhg Beirne.
Ireland coach Andy Farrell also makes two further changes to his pack with Ronan Kelleher and Jack Conan taking over from Rob Herring and Peter O'Mahony.
McCloskey has performed excellently in Ireland's opening two wins but Farrell has opted to give more game time to British and Irish Lion Aki given his lack of action for Connacht this season.
Second row Henderson will partner James Ryan, who takes the captaincy in Sexton's absence with regular deputy skipper O'Mahony dropping to the bench.
Kelleher starts at hooker after coming on in the first half of the thrilling win over France following the head knock suffered by Ulster's Rob Herring.
With Herring not named in the squad, Kelleher's Leinster team-mate, Dan Sheehan, who has emerged as first choice for Farrell over the last 12 months, is drafted into the replacements following his return after injury.
Conan's inclusion at number eight sees O'Mahony named in the replacements as Caelan Doris switches to blindside flanker following his man-of-the-match display against France.
Munster prop Dave Kilcoyne retains his bench spot despite Cian Healy's availability after injury while Jack Crowley will be fly-half back-up as he is preferred to Joey Carbery, who was drafted into the squad earlier this week after being left out for the opening games.
Italy make three changes from the 31-14 defeat by England which include fit-again fly-half Paolo Garbisi taking over from Harlequins' Tommaso Allan.
Pierre Bruno is recalled at left wing, Tommaso Menoncello switches to centre and Luca Morisi drops to the bench while coach Kieran Crowley drafts in Simone Ferrari at tighthead prop for Marco Riccioni.
Crowley's team includes 10 Benetton players, with London Irish prop Danilo Fischetti the only member of the starting pack who doesn't play for the Treviso-based club.
Ireland: Keenan; Hansen, Ringrose, Aki, Lowe; R Byrne, Casey; Porter, Kelleher, Bealham; Henderson, Ryan (capt); Doris, Van der Flier, Conan.
Replacements: D Sheehan, Kilcoyne, O'Toole, Baird, O'Mahony, Murray, Crowley, McCloskey.
Italy: Capuozzo; Padovani, Brex, Menoncello, Bruno; Garbisi, Varney; Fischetti, Nicotera, Ferrari, Cannone, Ruzza, Negri, Lamaro (capt), Cannone.
Replacements: Bigi, Zani, Riccioni, Iachizzi, Pettinelli, Fusco, Morisi, Allan.