Garry Ringrose will win his first Test cap when Ireland face Canada on Saturday – with another seven players in line to make their debut.
The hugely talented Leinster back, 21, will start at outside centre as boss Joe Schmidt changes his entire starting XV following last week's historic 40-29 win over New Zealand in Chicago.
Munster back-five forwards Billy Holland and Jack O'Donoghue will make their Test bows in the pack, with five potential debutants lying in wait on the bench.
Hooker James Tracy, prop John Ryan, flanker Dan Leavy, scrum-half Luke McGrath and wing Niyi Adeolokun are all now primed for their first taste of Test action this weekend.
Flanker Peter O'Mahony captains Schmidt's side in his first Test since tearing knee ligaments in Ireland's 24-9 World Cup victory over France in October 2015.
Leinster's bulldozing back-rower Sean O'Brien starts at openside in his first international since tearing a hamstring in February's 10-9 Six Nations defeat in France.
Head coach Schmidt omitted both O'Mahony and O'Brien from last weekend's Chicago trip, where Ireland claimed their first-ever win over New Zealand after 111 years of trying, ending the All Blacks' record 18-match winning run.
Schmidt hailed Ringrose as a "natural player" primed to transfer his free-running attacking game to the Test arena.
"He's given us confidence that he's ready and I don't doubt that he's ready to get started," said Schmidt.
"Garry's a really natural player. He sees things ahead of other people because of how well he reads the game. And he's defensively astute too."
Ireland: 15 Tiernan O'Halloran, 14 Craig Gilroy, 13 Garry Ringrose, 12 Luke Marshall, 11 Keith Earls, 10 Paddy Jackson, 9 Kieran Marmion; 1 Cian Healy, 2 Sean Cronin, 3 Finlay Bealham, 4 Ultan Dillane, 5 Billy Holland, 6 Peter O'Mahony (c), 7 Sean O'Brien, 8 Jack O'Donoghue.
Replacements: 16 James Tracy, 17 David Kilcoyne, 18 John Ryan, 19 Donnacha Ryan, 20 Dan Leavy, 21 Luke McGrath, 22 Joey Carbery, 23 Niyi Adeolokun.