Leinster hooker Gus McCarthy and Ulster flanker Cormac Izuchukwu will make their Test debuts among nine changes, two of them positional, after Ireland squeezed past Argentina 22-19 last Friday.
McCarthy captained Ireland to an U20 Six Nations Grand Slam last year. Izuchukwu became an Ulster regular last season and has been with the Ireland squad since the July tour of South Africa.
"(Izuchukwu has) been in around our squad for a while now," Ireland coach Andy Farrell said.
"The Emerging Ireland tour, the first tour (of South Africa in 2022), was when we first came across him. But the difference between the first tour and the second tour (this year) was like chalk and cheese.
"He was young on that first one but his ability, his point of difference with the maturity - he deserves a chance to show us what he's got."
As for McCarthy, Farrell said: "Rugby is a strange game. You think there's a pecking order and all of a sudden a kid gets an opportunity and shows up really well.
"We took him on the training week (in Portugal) as a development player and he showed up really well and he's forced our hand and deserves a shot as well."
Prendergast debuted in the Argentina win with 19 minutes to go, and will start this time, in place of a rested Jack Crowley. Scrumhalf Craig Casey, who played the last seven minutes, will also start, with Jamison Gibson-Park dropping out.
Bundee Aki has come back into the midfield for Garry Ringrose, and fullback Jamie Osborne has replaced Hugo Keenan to get his first start at home in his fifth Test. Left wing James Lowe has also been rested and Jacob Stockdale given a run for the first time since August 2023.
A much-changed bench includes Tom O'Toole, the tighthead prop who was concussed only two minutes into a replacement appearance against New Zealand two weeks ago, and Connacht back-rower Cian Prendergast and Ulster centre Stuart McCloskey, who last played for Ireland in Rugby World Cup warmups 15 months ago.
Tighthead prop Tadhg Furlong failed for another week to recover fully recover from a month-old hamstring injury.
Ireland: Jamie Osborne, Mack Hansen, Robbie Henshaw, Bundee Aki, Jacob Stockdale, Sam Prendergast, Craig Casey; Caelan Doris (capt), Josh van der Flier, Cormac Izuchukwu, Tadhg Beirne, Joe McCarthy, Finlay Bealham, Gus McCarthy, Andrew Porter. Replacements: Ronan Kelleher, Tom O'Toole, Thomas Clarkson, Iain Henderson, Cian Prendergast, Conor Murray, Ciaran Frawley, Stuart McCloskey.
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