Willie le Roux and Faf de Klerk have been named in South Africa's starting XV for the first Test against England at Ellis Park on Saturday.
Wasps full-back Le Roux and Sale scrum-half De Klerk have been star performers in the Aviva Premiership this season and, alongside Duane Vermeulen - who has just left Toulon - are the only European-based players present.
It will be the first time Le Roux and De Klerk have played for the Springboks since 2016.
Tendai Mtawarira, Bongi Mbonambi and Trevor Nyakane form South Africa"s first all-black starting front row, while blindside flanker Siya Kolisi is their first black Test captain.
Nyakane is carrying a rib injury, however, and will be replaced by Wilco Louw if he fails a fitness test on Friday.
S'busiso Nkosi and Aphiwe Dyantyi make their debuts on the wings and lock RG Snyman completes the trio of uncapped players picked.
The team is completely different to the one edged by Wales in Washington last Saturday, with Louw the sole survivor if Nyakane is declared unfit.
"We have some good experienced players and there are also some really exciting young men who have earned their opportunity to play," SA Rugby director of rugby Rassie Erasmus said.
"I'm especially pleased for the three newcomers, Aphiwe, Sbu and RG, and I am looking forward to see how they will perform in tough Test match conditions against a formidable opponent.
"England are a top-class, quality side and they will do doubt be very determined to be successful in this series, and with us desperate for success as well it means that the supporters can expect a really good Test match Saturday.
"We have prepared as well as we could and the players are looking forward to playing in front of our passionate supporters in Johannesburg."
South Africa team to face England in Saturday's first Test at Ellis Park, Johannesburg:
W le Roux (Wasps); S Nkosi (Sharks) L Am (Sharks), D de Allende (Stormers), A Dyantyi (Lions); H Pollard (Bulls), F de Klerk (Sale Sharks); T Mtawarira (Sharks), B Mbonambi (Stormers), T Nyakane (Bulls)/W Louw (Stormers), RG Snyman (Bulls), F Mostert (Lions), S Kolisi captain (Stormers), JL du Preez (Sharks), D Vermeulen (unattached).
Replacements: A van der Merwe (Sharks), S Kitshoff (Stormers), W Louw (Stormers)/T du Toit (Sharks), PS du Toit (Stormers), S Notshe (Stormers), I van Zyl (Bulls), E Jantjies (Lions), W Gelant (Bulls).