The Boks have brought Ruan Combrinck and Warren Whiteley into the starting line-up for Saturday's series decider against Ireland.
Combrinck, who came off the bench to score the try that triggered a dramatic second-Test comeback for a 32-26 triumph in Johannesburg, replaces JP Pietersen on the right wing.
Combrinck's performance last week earned him the man of the match award on debut, and his form has been rewarded by coach Allister Coetzee with a start in Port Elizabeth.
Pietersen moves to the left wing to accommodate Combrinck as Lwazi Mvovo, vulnerable under the high ball in the second Test, drops to the bench at the Nelson Mandela Bay Stadium.
The second Bok change was enforced, with No 8 Duane Vermeulen ruled out by an elbow injury. His place goes to Whiteley, who also scored a try at Ellis Park last week.
There are three changes to the bench with two uncapped forwards, France-based prop Steven Kitshoff and flanker Jaco Kriel, called up for the first time in the series.
Kitshoff replaces the injured Trevor Nyakane, while Kriel comes in to take up Whiteley's place on the bench.
Ireland were shock 26-20 winners of the first Test in Cape Town, after which South Africa won the second in Johannesburg thanks to a 22-point last-quarter onslaught.
Prior to the first Test South Africa had never lost to Ireland on home soil, and their fans were ruthless in their response in the second Test, booing their side off the field at half-time as they went into the break 19-3 down. South Africa did fight back, but their form has been far from that of the side that took third place at last year's World Cup.
The series decider throws everything on the line this Saturday, as the proud Boks look to avoid a series defeat to Schmidt's side.
South Africa: 15 Willie le Roux, 14 Ruan Combrinck, 13 Lionel Mapoe, 12 Damian de Allende, 11 JP Pietersen, 10 Elton Jantjies, 9 Faf de Klerk; 1 Tendai Mtawarira, 2 Adriaan Strauss (c), 3 Frans Malherbe, 4 Eben Etzebeth, 5 Pieter-Steph du Toit, 6 Francois Louw, 7 Siya Kolisi, 8 Warren Whiteley.
Replacements: 16 Bongi Mbonambi, 17 Steven Kitshoff, 18 Julian Redelinghuys, 19 Franco Mostert, 20 Jaco Kriel, 21 Rudy Paige, 22 Morne Steyn, 23 Lwazi Mvovo.
Watch the deciding Test between South Africa and Ireland live on Sky Sports 1 from 3.30pm on Saturday. Catch the match for £6.99 with a NOW TV day pass.