Up front Ospreys pair Huw Bennett and Adam Jones come into the front row to replace Dragons hooker Lloyd Burns and Exeter Chiefs bound prop Craig Mitchell respectively, with Burns moving to the bench.
In the backs Scarlets centre Jonathan Davies continues his established midfield partnership with Jamie Roberts (Blues), a combination that was temporarily split up in that England match to accommodate the now injured Gavin Henson.
Davies and Roberts were reunited a week later when Wales beat Argentina (28-13) at the Millennium Stadium in their final match on home soil before leaving for New Zealand, a match which also featured Blues wing Leigh Halfpenny, Scarlets scrum-half Tavis Knoyle, Blues second row Bradley Davies and, from the bench, Ospreys prop Ryan Bevington.
Halfpenny, Knoyle, Davies and Bevington all join Burns in providing cover from the bench against the Springboks and are joined by Scarlets centre Scott Williams, Sales Sharks back row Andy Powell.
Bayonne-bound scrum-half Mike Phillips reforms his half-back partnership with Scarlet Rhys Priestland. An exciting back three of James Hook (Perpignan), George North (Scarlets) and Shane Williams (Ospreys) completes the backline.
Up front the established back row of captain Sam Warburton (Blues), Dan Lydiate and Toby Faletau (Dragons) is retained, another Dragon Luke Charteris partners Osprey Alun Wyn Jones at lock and prop Paul James (Ospreys) completes the starting line-up.
"We are going into this game looking for a win," said Wales coach Warren Gatland. If you get the world champions in your pool you want to play them first up and throw everything you've got at them.
"We've got the toughest group in the competition, but we know if we can come through we will be in good shape. The players have done everything we have asked of them so far, they have worked incredibly hard."
WALES: James Hook; George North, Jonathan Davies, Jamie Roberts, Shane Williams, Rhys Priestland, Mike Phillips; Paul James, Huw Bennett, Adam Jones, Luke Charteris, Alun Wyn Jones, Dan Lydiate, Sam Warburton (capt), Toby Faletau.
REPLACEMENTS: Lloyd Burns, Ryan Bevington, Bradley Davies, Andy Powell, Tavis Knoyle, Scott Williams, Leigh Halfpenny.