Ireland head coach Joe Schmidt has made five changes to his starting line-up that beat South Africa 26-20 in Cape Town last weekend.
Former Stormers lock Quinn Roux will make his first start for Ireland against the country of his birth at Ellis Park on Saturday as Iain Henderson will move to the blindside flank as Rhys Ruddock takes over at openside.
Conor Murray and Paddy Jackson are retained at half-back, while Robbie Henshaw is joined in the centre by Ulster's Stuart Olding, who is set for his first start since his debut against the USA three years ago. Henshaw also made his international bow that night in Houston.
Craig Gilroy is introduced on the left wing for his eighth cap, making it an all-Ulster back-three alongside Andrew Trimble and full-back Jared Payne.
Sean Reidy and Tiernan O'Halloran are the two uncapped players on the bench and they are joined by Richardt Strauss, Dave Kilcoyne, Finlay Bealham, Donnacha Ryan, Kieran Marmion and Ian Madigan.
Ireland: 15 Jared Payne, 14 Andrew Trimble, 13 Robbie Henshaw, 12 Stuart Olding, 11 Craig Gilroy, 10 Paddy Jackson, 9 Conor Murray, 8 Jamie Heaslip, 7 Rhys Ruddock, 6 Iain Henderson, 5 Quinn Roux, 4 Devin Toner, 3 Tadhg Furlong, 2 Rory Best, 1 Jack McGrath
Replacements: 16 Richardt Strauss, 17 David Kilcoyne, 18 Finlay Bealham, 19 Donnacha Ryan, 20 Sean Reidy, 21 Kieran Marmion, 22 Ian Madigan, 23 Tiernan O’Halloran
Date: Saturday, June 18
Venue: Ellis Park, Johannesburg
Kick-off: 17:00 local (15:00 GMT)
Referee: Angus Gardner (Australia)
Assistant Referees: Glen Jackson (New Zealand), Ben Whitehouse (Wales)
TMO: Jim Yuille (Scotland)