Jacob Stockdale will make his first Ireland appearance on home soil against South Africa on Saturday in Dublin.
The Ulster wing is joined in a new-look back-line by debutant Bundee Aki, with Andrew Conway replacing the injured Keith Earls in the opening autumn Test.
Stockdale made his debut against US Eagles in the summer and has scored five tries for Ulster this season.
New Zealand-born Aki earns his first Ireland cap after recently qualifying under the three-year residency rule.
His inclusion means there is no place in the match-day squad for Ulster’s Stuart McCloskey or Munster’s Chris Farrell.
The Connacht centre’s promotion to the national team has provoked a lot of debate regarding the residency rule, which World Rugby have recently extended from three to five years.
Ireland head coach Joe Schmidt admitted he has sympathy for the player at the centre of the storm.
“Sometimes where you are born is less relevant to where you have invested in the last period of time and I think Bundee has invested incredibly well in the west,” said Schmidt.
“They have benefited from his experience, his commitment and his durability. Bundee has played an immense amount of minutes for Connacht.
“It’s an unfortunate distraction. I do feel sympathy for Bundee. He’s just doing what he loves doing and what he’s very good at, but we hope it doesn’t distract him.
“There’s no question in the group’s mind. They’re excited to have him in the group.”
Schmidt favours form
Schmidt confirmed that Earls, who picked up a training ground injury, is a doubt for the entire autumn series.
Ireland play Fiji and Argentina on 18 and 25 November respectively.
Cian Healy steps in to the front row for Jack McGrath, who picked up a hip injury in training while CJ Stander lines up against his native country in the back row.
Darren Sweetnam is poised to earn his first cap off the bench.
Schmidt explained: “We were looking for form players. We wanted to reward players who were playing well for their provinces and we also wanted experience. I think we have both.”
Ireland XV: Rob Kearney; Andrew Conway, Robbie Henshaw, Bundee Aki, Jacob Stockdale; Jonny Sexton, Conor Murray; Cian Healy, Rory Best (capt), Tadhg Furlong, Iain Henderson, Devin Toner, Peter O’Mahony, Sean O’Brien, CJ Stander
Replacements: Rob Herring, Dave Kilcoyne, John Ryan, James Ryan, Rhys Ruddock, Kieran Marmion, Joey Carberry, Darren Sweetnam