Sibusiso Nkosi, Aphiwe Dyantyi and RG Snyman will make their Springbok debuts on Saturday when South Africa face England in the opening Test in Johannesburg on Saturday.
The team is a completely revamped combination from the side that lost to Wales in Washington D.C. last weekend, and will be skippered by new captain in Siya Kolisi.
Wilco Louw is only player to be retained, should Trevor Nyakane fail to recover from a rib injury. He has been bracketed with Louw in the starting XV and was given until Friday to recover from the knock.
Experienced fullback Willie le Roux makes a return to the side, behind the two uncapped wingers in Nkosi and Dyantyi, while Faf de Klerk is coach Rassie Erasmus' scrumhalf of choice.
De Klerk and Le Roux haven't played for the Boks since 2016, but after fine seasons for their clubs the duo is back in the run-on side.
Handré Pollard will start at flyhalf, while Duane Vermeulen (number 8) teams up with Jean-Luc du Preez and captain Kolisi in the loose forward combination.
The uncapped Snyman earns his first Springbok cap as lock partner to the industrious Franco Mostert, while Pieter-Steph du Toit will play off the bench.
Tendai Mtawarira (prop) is now just one Test away from a century of Springbok caps after he was named to start next to Bongi Mbonambi in the front row.
"We have some good experienced players while there are some really exciting young men who have earned their opportunity to play for the Springboks," Erasmus said in a SA Rugby press release.
"I am 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."
According to Erasmus his side knows what to expect from England, whom he described as a very well-drilled team under the leadership of Eddie Jones.
"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," Erasmus added..
"We have prepared as well as we could and the players are looking forward to playing in front of our passionate supporters in Johannesburg."
The Springbok team to face England (in order of name, franchise/club, caps and points - tries, penalties, conversions, drop goals):
15. Willie le Roux (Wasps, England, 41, 50 - 10t)
14 S'busiso Nkosi (Cell C Sharks, uncapped)
13. Lukhanyo Am (Cell C Sharks, 1, 0)
12. Damian de Allende (DHL Stormers, 28, 15 - 3t)
11. Aphiwe Dyantyi (Emirates Lions, uncapped)
10. Handré Pollard (Vodacom Bulls, 26, 218 - 3t, 37c, 40p, 3d)
9. Faf de Klerk (Sale Sharks, England, 11, 0)
8. Duane Vermeulen (Unattached, 39, 10 - 2t)
7. Jean-Luc du Preez (Cell C Sharks, 10, 10 - 2t)
6. Siya Kolisi captain (DHL Stormers, 28, 20 - 4t)
5. Franco Mostert (Emirates Lions, 18, 5 - 1t)
4. RG Snyman (Vodacom Bulls, uncapped)
3. Trevor Nyakane (Vodacom Bulls 36, 5 - 1t) / Wilco Louw (DHL Stormers, 6, 0)
2. Bongi Mbonambi (DHL Stormers, 14, 5 - 1t)
1. Tendai Mtawarira (Cell C Sharks, 98, 10, 2 - 1t)
16. Akker van der Merwe (Cell C Sharks, 1, 0)
17. Steven Kitshoff (DHL Stormers, 24, 5 - 1t)
18. Wilco Louw (DHL Stormers, 6, 0) / Thomas du Toit (Cell C Sharks, 1, 0)
19. Pieter-Steph du Toit (DHL Stormers, 33, 20 - 4t)
20. Sikhumbuzo Notshe (DHL Stormers, 1, 0)
21. Ivan van Zyl (Vodacom Bulls, 1, 0)
22. Elton Jantjies (Emirates Lions, 24, 210 - 2t, 40c, 40p)
23. Warrick Gelant (Vodacom Bulls, 2, 5 - 1t)