Adam Jones will make his 100th International appearance in the game at Growthpoint Kings Park in Durban, in a match that will be his 95th cap for Wales (five appearances for the British and Irish Lions).
Gatland has also named two uncapped players in his match day squad, Scarlets scrum-half Gareth Davies and Ospreys' Matthew Morgan, who both impressed in recent outings, named as replacements.
At half-back Mike Phillips and Dan Biggar continue their partnership, as do Jamie Roberts and Jonathan Davies in the midfield.
British and Irish Lions, George North and Alex Cuthbert line-up on the wings with Liam Williams starting at full-back, in the back three.
Adam Jones is joined in the front-row by Gethin Jenkins, who will be making a record 106th appearance for Wales, and Ken Owens.
Luke Charteris will partner Captain Alun Wyn Jones in the second-row with Aaron Shingler joining Dan Lydiate and Taulupe Faletau in the back-row.
"We started the tour well on Tuesday against EP Kings but it's important we go out on Saturday and perform to the level we know we can,” said Gatland.
"A test series in South Africa is always a tough challenge, but we are excited by it and looking forward to getting out there on Saturday.
"A lot of this side have experienced playing over here before in big games and this week is no different, it's going to be a brilliant occasion, the atmosphere will be electric and hopefully it will be a great test match.
"As coaches we have been impressed in training over the last couple of weeks and there were a couple of tough calls to make but it's great guys like Gareth and Matthew have a chance after putting their hands up.”
Matthew Rees' remarkable return is capped with a place in the Test squad and he features on the bench will fellow front-row replacements Paul James and Samson Lee. Ian Evans and Josh Turnbull complete the forward contingent with James Hook joining Davies and Morgan as cover for the backline.
Wales Squad to Face South Africa:
Liam Williams (Scarlets), Alex Cuthbert (Cardiff Blues), Jonathan Davies
(Scarlets), Jamie Roberts (Racing Metro), George North (Northampton Saints),
Dan Biggar (Ospreys), Mike Phillips (Racing Metro), Gethin Jenkins (Cardiff
Blues), Ken Owens (Scarlets), Adam Jones (Ospreys), Luke Charteris (Perpignan),
Alun Wyn Jones (Capt) (Ospreys), Dan Lydiate (Racing Metro), Aaron Shingler
(Scarlets), Taulupe Faletau (Newport
Gwent Dragons).
Replacements: Matthew Rees (Cardiff Blues), Paul James (Bath), Samson Lee (Scarlets), Ian Evans (Ospreys), Josh Turnbull (Scarlets), Gareth Davies (Scarlets), James Hook (Perpignan), Matthew Morgan (Ospreys).
