Bundee Aki will make his Ireland debut against South Africa on Saturday, forging a potent centre pairing with Robbie Henshaw.
Connacht's New Zealand-born midfielder has been thrust into immediate Test action after completing his three-year residency qualification.
Ulster flyer Jacob Stockdale will win his third cap, with the physical 21-year-old cutting an imposing figure on the wing.
Injuries to Garry Ringrose and Jared Payne have opened the door for Aki to make his first Test start, and the 27-year-old of Samoan parentage is expected to add extra steel to Ireland's midfield.
Keith Earls has been ruled out late on due to a suspected hamstring problem, with Munster team-mate Andrew Conway stepping onto the wing.
Darren Sweetnam could also make his Test debut from the bench.
Aki and Henshaw excelled in tandem when Connacht won the PRO12 title in 2016, and will now reprise that partnership in the Test arena.
Rob Kearney will start at full-back in his first Test since the Six Nations, while Cian Healy will step up to start with Jack McGrath having picked up a knock in training.
Here's your Ireland team for the 1st #GuinnessSeries match v @Springboks #TeamOfUs #IREvRSA pic.twitter.com/SxV7Jodk78
— Irish Rugby (@IrishRugby) November 9, 2017
Head coach Joe Schmidt confirmed Earls' hamstring problem, and admitted the Munster stalwart could miss the entire three-match autumn series.
"Keith picked up the injury on Tuesday, and it was a surprise to him and us," said Schmidt.
"It's a hamstring injury, and I think it's going to make it certainly a struggle for next week, and potentially the week after.
"So he will be a doubt for the series at this point.
"We're disappointed and so is he; he was sensational for us in Japan in the summer.
"Not only his on-field actions but the way he led the young players, that was another role he had fully embraced in this camp.
"He's the consummate professional, a class player, that rapid acceleration.
"But what a fantastic chance for Andrew Conway and Darren Sweetnam."
Ireland team to play South Africa
Forwards: 1 Cian Healy, 2 Rory Best (Captain), 3 Tadhg Furlong, 4 Iain Henderson, 5 Devin Toner, 6 Peter O'Mahony, 7 Sean O'Brien, 8 CJ Stander
Backs: 9 Conor Murray, 10 Johnny Sexton, 11 Jacob Stockdale, 12 Bundee Aki*, 13 Robbie Henshaw, 14 Andrew Conway, 15 Rob Kearney
Replacements: 16 Rob Herring, 17 Dave Kilcoyne, 18 John Ryan, 19 James Ryan, 20 Rhys Ruddock, 21 Kieran Marmion, 22 Joey Carbery, 23 Darren Sweetnam*
* denotes uncapped player