The Boks face Samoa at Villa Park in Birmingham on Saturday; kick-off is scheduled for 5.45pm.
In a surprising move in the front-row, Bismarck du Plessis is completely demoted from the match-day squad with Adriaan Strauss earning promotion from the bench to earn his 50th cap.
In the rest of the pack, Eben Etzebeth returns to the starting XV in place of Lood de Jager while incumbent No. 8 Duane Vermeulen makes his long-awaited return.
Vermeulen, the current South African Rugby player of the Year, will be featuring in his first Test of 2015 after going under the knife for neck repairing.
In the backs, mercurial fullback Willie le Roux makes a return to anchor the back three including Bryan Habana and the returning JP Pietersen.
Inside centre Damian de Allende will be making his World Cup bow in place of Jesse Kriel, who drops to the bench. Captain Jean de Villiers moves outside to accommodate De Allende at 13.
Influential scrumhalf Fourie du Preez also makes his return from a lengthy injury in a new halfback pairing along Handre Pollard.
“It’s been a very tough week after the massive disappointment of last weekend and we owe our supporters a winning performance on Saturday,” said Meyer.
“The last few days have been a time for retrospection and the team this week has been selected specifically with Samoa in mind, as we know we’ll have to be at our very best to succeed.
“They will pose a massive challenge and I think it’s fair to say that it’s the biggest game of the season for us. They have a very strong team with players plying their trade all over the world.
“Four years ago in the World Cup pool match in New Zealand, the Samoans pushed the Boks close and we’re expecting more of the same this weekend. It will be brutally physical and we have to be 100 per cent focused and ready.”
15 Willie le Roux, 14 JP Pietersen, 13 Jean de Villiers (captain), 12 Damian de Allende, 11 Bryan Habana, 10 Handre Pollard, 9 Fourie du Preez, 8 Duane Vermeulen, 7 Schalk Burger, 6 Francois Louw, 5 Victor Matfield, 4 Eben Etzebeth, 3 Jannie du Plessis, 2 Adriaan Strauss, 1 Beast Mtawarira
Substitutes: 16 Schalk Brits, 17 Trevor Nyakane, 18 Frans Malherbe, 19 Lood de Jager, 20 Siya Kolisi, 21 Ruan Pienaar, 22 Pat Lambie, 23 Jesse Kriel – @SabeloBoksburg