Hallam Amos, Elliot Dee, Cory Hill, Ross Moriarty and Aaron Wainwright have been named in the side.
Cardiff Blues' Ellis Jenkins will captain Wales for the first time on Saturday when he leads his country against South Africa in Washington D.C.
The former Wales U20 skipper will line up alongside Seb Davies and Ross Moriarty in the back-row as Wales take on the Springboks in their opening summer tour encounter.
Nicky Smith, Elliot Dee and Dillon Lewis start in the front-row with Bradley Davies and Cory Hill packing down in the second-row.
Owen Watkin and George North are named in the centre, with North making his 4th start in the midfield for Wales.
Scarlets pair Steff Evans and Tom Prydie are named on the wing with Prydie making his first international appearance since the summer of 2013. Hallam Amos starts at full-back.
“Saturday is a huge opportunity for this squad and for players individually,” said Wales head coach Warren Gatland.
“Everything we are doing is geared for the RWC in 15 months’ time and the next three matches are a hugely important part of our development.
“This weekend is an opportunity for players to build on their test rugby experience and lay a marker down for the jersey and for the position going forward.
“I think there are exciting selections across the team and I’m looking forward to Saturday to see what we are able to do against the Springboks.”
Ryan Elias, Wyn Jones and Rhodri Jones provide the forward cover on the bench. Adam Beard and uncapped flanker Aaron Wainwright complete the forward contingent. Aled Davies, Rhys Patchell and Hadleigh Parkes are named as the backline cover. (Patchell will undergo a fitness test ahead of the game with Gareth Davies providing cover if he does not come through the session).
WALES TEAM TO PLAY SOUTH AFRICA
(Saturday, June 2 KO 17:00 local – live on Channel 4)
15. Hallam Amos (15 Caps)
14. Tom Prydie (7 Caps)
13. George North (73 Caps)
12. Owen Watkin (4 Caps)
11. Steff Evans (9 Caps)
10. Gareth Anscombe (15 Caps)
9. Tomos Williams (*Uncapped)
1. Nicky Smith (18 Caps)
2. Elliot Dee (7 Caps)
3. Dillon Lewis (2 Caps)
4. Bradley Davies (62 Caps)
5. Cory Hill (15 Caps)
6. Seb Davies (4 Caps)
7. Ellis Jenkins (6 Caps) (CAPT)
8. Ross Moriarty (20 Caps)
Replacements:
16. Ryan Elias (2 Caps)
17. Wyn Jones (8 Caps)
18. Rhodri Jones (16 Caps)
19. Adam Beard (2 Caps)
20. Aaron Wainwright (*Uncapped)
21. Aled Davies (8 Caps)
22. Rhys Patchell (8 Caps) / Gareth Davies (32 Caps)
23. Hadleigh Parkes (6 Caps)
