The 2019 and 2023 Rugby World Cup winner got the nod ahead of fellow forwards Bongi Mbonambi and Eben Etzebeth for the Springboks' first match since winning the World Cup in France last October.
Du Toit will be hoping for better luck against Wales in London this weekend as he led South Africa in a narrow defeat to the Welsh, also in a season opener, six years ago in Rassie Erasmus' first game in charge.
Du Toit is captaining the record four-time world champions as the Test is being played outside the international window, which bars France-based regular captain Siya Kolisi.
"This is an exciting playing squad," said head coach Erasmus ahead of South Africa's 13-Test season.
"We are looking forward to seeing how the uncapped players step up at top international level and how we execute what we have been working on at training in the last few days.
"The likes of Edwill, Jordan, Ben-Jason, and Sacha have really impressed us at training, and we believe they have what it takes to make their presence felt against a quality team such as Wales.
"They will be surrounded by several experienced campaigners - some of whom are Rugby World Cup winners - so they will have enough guidance on the field to fulfil their roles.
"It is equally exciting for us to see players such as Aphelele (Fassi), Evan (Roos), Ntuthuko (Mchunu), and Salmaan (Moerat) back in the green in gold."
Club commitments, injuries and a suspension left Erasmus with only 10 of the 2023 World Cup final squad to consider for the Twickenham Test.
He included seven in his starting line-up and the other three are on the bench. Erasmus also chose four uncapped players, with two set to start.
The starters from the 12-11 World Cup final victory over New Zealand include backs Jesse Kriel and Faf de Klerk and forwards Ox Nche, Etzebeth, Franco Mostert, Kwagga Smith and Du Toit.
Back Damian de Allende and forwards Mbonambi and Frans Malherbe are among the replacements as the Springboks seek a third straight victory over Wales.
Winger Edwill van der Merwe and fly-half Jordan Hendrikse are the new caps who will start, and back Sacha Feinberg-Mngomezulu and loose forward Ben-Jason Dixon could debut off the bench.
South Africa are using the Wales Test to prepare for a blockbuster two-Test home series against Ireland in July.
The Irish, ranked second in the world behind South Africa, were the only team to beat the Springboks at the 2023 World Cup, winning a pool match 13-8 in Paris.
South Africa (15-1)
Aphelele Fassi; Edwill van der Merwe, Jesse Kriel, Andre Esterhuizen, Makazole Mapimpi; Jordan Hendrikse, Faf de Klerk; Evan Roos, Pieter-Steph du Toit (capt), Kwagga Smith; Franco Mostert, Eben Etzebeth; Vincent Koch, Malcolm Marx, Ox Nche
Replacements: Bongi Mbonambi, Ntuthuko Mchunu, Frans Malherbe, Salmaan Moerat, Ben-Jason Dixon, Grant Williams, Sacha Feinberg-Mngomezulu, Damian de Allende
