Scarlets number ten Rhys Priestland has won the fly-half shootout with James Hook and Dan Biggar to start against South Africa.
Perpignan star Hook is named amongst the replacements, whilst Ospreys' fly-half Dan Biggar misses out on a spot in the matchday 23.
George North has been selected on the right wing in place of the injured Alex Cuthbert, with uncapped Ospreys sensation Eli Walker picked on the opposite flank.
Sam Warburton captains Wales from openside flanker, combining with two other British and Irish Lions in Toby Faletau and Dan Lydiate in the back-row, with Bradley Davies in the second row alongside Alun Wyn Jones.
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.
The match against South Africa is the first of four November 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 are 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: 15 Leigh Halfpenny, 14 George North, 13 Jonathan Davies, 12 Scott Williams, 11 Eli Walker, 10 Rhys Priestland, 9 Mike Phillips, 8 Toby Faletau, 7 Sam Warburton (c), 6 Dan Lydiate, 5 Alun Wyn Jones, 4 Bradley Davies, 3 Adam Jones, 2 Richard Hibbard, 1 Gethin Jenkins.
Replacements: 16 Ken Owens, 17 Paul James, 18 Scott Andrews, 19 Luke Charteris, 20 Justin Tipuric, 21 Lloyd Williams, 22 James Hook, 23 Liam Williams.
Date: Saturday, November 9
Kick-off: 17:30 GMT
Venue: Millennium Stadium, Cardiff
Referee: Alain Rolland (Ireland)
Assistant Referees: George Clancy (Ireland), Marius Mitrea (Italy)
TMO: Eric Gauzins (France)