Tiernan O'Halloran will replace the injured Jared Payne at full-back for Ireland's series decider against South Africa in Port Elizabeth on Saturday.
O'Halloran came off the bench for his debut last week and the Connacht back has been handed the No 15 jersey after Payne was ruled out with a calf injury.
Joe Schmidt makes five changes and one positional switch to the team that suffered a dramatic late collapse at Ellis Park, with CJ Stander named in the back row after serving a one-match suspension for his dismissal in the first Test.
Stander starts alongside Jordi Murphy, who is preferred to Rhys Ruddock at openside, while Iain Henderson moves back into the second row to partner Devin Toner. Mike Ross replaces Tadhg Furlong at tighthead.
Luke Marshall comes in for the injured Robbie Henshaw at outside centre with Ulster team-mate Stuart Olding at 12, while Conor Murray will win his 50th cap as he continues his impressive half-back partnership with Paddy Jackson.
Craig Gilroy loses out to Keith Earls on the left wing with the uncapped Matt Healy named on a strong bench that includes Furlong, Ultane Dillane and Ruddock.
Eoin Reddan is also among the replacements in what will be his final appearance before retiring from rugby.
Ireland can clinch their first series victory over the Springboks in South Africa with a win at the Nelson Mandela Bay Stadium.
Ireland: 15 Tiernan O'Halloran, 14 Andrew Trimble, 13 Luke Marshall, 12 Stuart Olding, 11 Keith Earls, 10 Paddy Jackson, 9 Conor Murray; 1 Jack McGrath, 2 Rory Best (c), 3 Mike Ross, 4 Iain Henderson, 5 Devin Toner, 6 CJ Stander, 7 Jordi Murphy, 8 Jamie Heaslip.
Replacements: 16 Sean Cronin, 17 Finlay Bealham, 18 Tadhg Furlong, 19 Ultan Dillane, 20 Rhys Ruddock, 21 Eoin Reddan, 22 Ian Madigan, 23 Matt Healy.
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