Devin Toner will win his 50th cap when Ireland face Japan in Tokyo on Saturday, while John Cooney is set to make his debut as a replacement.
Toner, who made his debut against Samoa in November 2010, is set for his 50th Test appearance in the second row.
He is the eighth lock to hit the half-century for Ireland, joining a select group which includes Moss Keane, Donal Lenihan, Paddy Johns, Willie John McBride, Malcolm O'Kelly, Donncha O'Callaghan and Paul O'Connell.
Toner will be joined in the engine room by Kieran Treadwell who won his first cap off the bench during last week's 50-22 win over Japan. At 21, he is Ireland's second youngest starting lock of the professional era. Bob Casey, who made his bow against England in 2000, beats him by just 28 days.
Irelnd head coach Joe Schmidt has made six changes in personnel for the rematch with the Brave Blossoms, along with two positional switches. Treadwell and Leinster hooker James Tracy come in for their first starts up front.
The side is captained again by Rhys Ruddock who is joined in an all-Leinster back row by number eight Jack Conan, who has scored in both tour games so far, and Josh van der Flier who returns at openside flanker.
Tracy, Cian Healy, who is set for his 70th cap, and John Ryan, who will make his third start of the tour, will join forces in the front row. That means the Munster tighthead will have played in all eight of Ireland's Tests in 2017, including five appearances as a replacement during the Six Nations.
The selected back-line sees Ulster duo Luke Marshall and Jacob Stockdale slot back in at outside centre and on the left wing respectively. Marshall pairs up with Garry Ringrose, while Stockdale's inclusion sees record breaker Keith Earls revert to the right wing and Andrew Conway takes over the full-back position vacated by Simon Zebo.
Paddy Jackson, who has scored 185 points in his Ireland career to date, will win his 25th cap this weekend when he starts at fly-half alongside Connacht's Kieran Marmion.
Marmion's fellow scrum-half John Cooney could become the eighth and final debutant of the tour. He is listed on a bench which also contains brothers Niall and Rory Scannell, Dave Kilcoyne, Andrew Porter, James Ryan, Sean Reidy, who is set to add to his first cap won a year ago in South Africa, and Tiernan O'Halloran.
Ireland: 15 Andrew Conway, 14 Keith Earls, 13 Garry Ringrose, 12 Luke Marshall, 11 Jacob Stockdale, 10 Paddy Jackson, 9 Kieran Marmion, 8 Jack Conan, 7 Josh van der Flier, 6 Rhys Ruddock (c), 5 Devin Toner, 4 Kieran Treadwell, 3 John Ryan, 2 James Tracy, 1 Cian Healy
Replacements: 16 Niall Scannell, 17 Dave Kilcoyne, 18 Andrew Porter, 19 James Ryan, 20 Sean Reidy, 21 John Cooney, 22 Rory Scannell, 23 Tiernan O'Halloran
Date: Saturday, June 24
Venue: Ajinomoto Stadium, Tokyo
Kick-Off: 14:40 local (05:40 GMT)
Referee: JP Doyle (England)
Assistant Referees: Mathieu Raynal (France), Alex Ruiz (France)
TMO: Glenn Newman (New Zealand)