Cardiff Blues pair Leigh Halfpenny and Andy Powell will make their Wales debuts in Saturday's Millennium Stadium clash against world champions South Africa.
Halfpenny, 19, replaces injured Scarlets wing Mark Jones, while number eight Powell packs down in the back row alongside his Blues colleague Martyn Williams and skipper Ryan Jones.
Ospreys hooker Huw Bennett, who was injured on EDF Energy Cup duty two days ago, is another absentee, with Scarlets’ Matthew Rees starting in the number two shirt.
And Wales head coach Warren Gatland has sprung a surprise at scrum-half, preferring Gloucester’s Gareth Cooper to the more experienced Dwayne Peel, who has to content himself with a place on the bench.
Behind the scrum, Gavin Henson and Jamie Roberts forge a new-look centre combination - Roberts has already played wing and full-back in his short Test career - while Stephen Jones edges out James Hook for fly-half duties.
There are eight changes from Wales’ last game - a 37-21 defeat against the Springboks in Pretoria almost five months ago - with Henson making a first Test start since the RBS 6 Nations title and Grand Slam-clinching victory over France in March.
Ospreys prop Adam Jones, meanwhile, wins his 50th cap, making him the 23rd Welsh player to reach that landmark.
Halfpenny, a member of the Wales Under-20 World Cup squad this summer, has taken senior rugby by storm.
He has scored seven tries in just seven appearances for the Blues, including three during their current Heineken Cup campaign.
The 27-year-old Powell, meanwhile, has waited far longer for his international opportunity during a career that saw him play for Newport, Beziers, Leicester and the Scarlets before linking up with the Blues.
He has also recovered from reconstruction surgery on both shoulders during the past two years, and he goes into the autumn Test series opener as Welsh rugby’s form number eight.
Gatland said: “Both of the debutants have been form players so far this season, so they now get a chance to test themselves against the very best team in the world.
“At 19-years-old, our message to Leigh has been to just go out there and enjoy himself. He needs to play without fear and enjoy the experience.
“Andy Powell is a little different. He has been around for a while and is an experienced head, despite his lack of international caps.
“But he is most definitely in form. We will be looking to get the ball in his hands and see him run.
“Ryan Jones is adept on either side of the scrum, but to switch our captain (from number eight) does tell you a little bit about what we think of Andy.
“At scrum-half, Gareth Cooper is the man in possession of the shirt after doing well for us, particularly in the second Test on tour this summer, and he has been rewarded.”
Wales have only beaten the Springboks once in 22 attempts, with South Africa chasing a 10th successive victory over the reigning RBS 6 Nations champions.
L Byrne (Ospreys); L Halfpenny (Cardiff Blues), J Roberts (Cardiff Blues), G Henson (Ospreys), S Williams (Ospreys); S Jones (Scarlets), G Cooper (Gloucester); G Jenkins (Cardiff Blues), M Rees (Scarlets), A Jones (Ospreys), A-W Jones (Ospreys), I Evans (Ospreys), R Jones (Ospreys, capt), M Williams (Cardiff Blues), A Powell (Cardiff Blues).
R Hibbard (Ospreys), Duncan Jones (Ospreys), I Gough (Ospreys), Dafydd Jones (Scarlets), D Peel (Sale Sharks), J Hook (Ospreys), T Shanklin (Cardiff Blues).