Walker will make his debut in a side which sees the return from injury of 2012 Grand Slam winning fly-half Rhys Priestland (Scarlets), and flanker Dan Lydiate (Racing Metro), who lines up for Wales for the first time since the summer of 2012.
Cardiff Blues prop Gethin Jenkins will win his 99th cap and is joined in the front row by the experienced duo of Richard Hibbard and Adam Jones (both Ospreys).
Bradley Davies (Blues) joins Alun Wyn Jones (Ospreys) in the second-row and the back-row is an all British and Irish Lions’ affair with Lydiate playing alongside Captain Sam Warburton (Blues) and Dragons’ Toby Faletau.
Mike Phillips will partner Priestland at half-back and the midfield is made up of the Scarlets centre pairing of Scott Williams and Jonathan Davies.
Walker, 21, is joined by George North (Northampton Saints) on the wing, who himself made his debut against the Springboks three years ago, scoring a brace of tries. Cardiff Blues full-back Leigh Halfpenny wears 15.
The match against South Africa is the first of four autumn games at the Millennium Stadium and head coach Warren Gatland knows it is going to be a huge encounter on Saturday.
“We always say we like to test ourselves against the best and Saturday is going to be just that with a huge game against South Africa first up,” said Gatland.
“The Springboks arrive in the UK off the back of their impressive Rugby Championship campaign and we know that we need to start well on Saturday.
“We go into the series as Six Nations Champions but we are looking forward to testing ourselves against the southern hemisphere sides and showing what we can do.
“Since we have been together, competition in the squad has been good and it is great to have both Rhys and Dan back available for us.
“Eli has impressed for his Region and whilst with us and it’s a great opportunity for him to make his mark in a very experienced side.”
WALES TEAM TO FACE SOUTH AFRICA:
Leigh Halfpenny (Blues), George North (Northampton Saints), Jonathan Davies (Scarlets), Scott Williams (Scarlets), Eli Walker (Ospreys), Rhys Priestland (Scarlets), Mike Phillips (Unattached), Gethin Jenkins (Blues), Richard Hibbard (Ospreys), Adam Jones (Ospreys), Bradley Davies (Blues), Alun Wyn Jones (Ospreys), Dan Lydiate (Racing Metro), Sam Warburton (Blues, Capt), Toby Faletau.
Replacements: Ken Owens (Scarlets), Paul James (Bath), Scott Andrews (Blues), Luke Charteris (Perpignan), Justin Tipuric (Ospreys) Lloyd Williams (Blues), James Hook (Perpignan), Liam Williams (Scarlets).
