Stanley made his test debut only in November, but head coach Stephen Betham said the 25-year-old directed the team well during the Pacific Nations Cup and has proven himself more than capable of stepping up to the first five-eight duties.
He also slotted a crucial penalty in their victory over the United States last weekend, after Pisi had struggled with the boot.
The other changes are in the forwards, with hooker Motu Matu'u and prop Census Johnston starting in place of Ole Avei and Anthony Perenise.
TJ Ioane will make his World Cup debut on the blindside flank, in place of the injured Maurie Fa'asavalu.
Fa'asavalu and Fa'atoina Autagavaia have been ruled out with calf strains, with George Pisi coming onto the bench, which means the Samoa side could feature three brothers at the same time.
Eight players in the Manu team were involved in Samoa's most recent clash against the Springboks, a 56-23 defeat in Pretoria two years ago, while 10 were involved when the teams squared off at the last World Cup four years ago.
Saturday's clash will be the fifth between Samoa and South Africa at a World Cup.
The Springboks made eight changes to their team, following their shock defeat to Japan last weekend.
Samoa squad: 1. Sakaria Taulafo, 2. Motu Matu'u, 3. Census Johnston, 4. Teofilo Paulo, 5. Iosefa Tekori, 6.TJ Ioane, 7.Jack Lam, 8.Ofisa Treviranus (c), 9.Kahn Fotuali'I, 10.Mike Stanley, 11 Alesana Tuilagi, 12 Rey Lee-Lo, 13 Paul Perez, 14 Ken Pisi, 15 Tim Nanai-Williams
Reserves: 16 Ole Avei, 17 Viliamu Afatia, 18 Anthony Perenise, 19 Faifili Levave, 20 Vavae Tuilagi, 21 Vavao Afemai, 22 Tusi Pisi, 23 George Pisi