Delve will start at number eight, captain Ryan Jones switching to six with Jonathan Thomas moving across to the open-side.
Blues hooker T Rhys Thomas will sit on the bench at Loftus Versfeld, having been called up this week for Rees, who injured his calf in the Bloemfontein mauling.
Wales have been put through brutal training sessions since, and delayed their team selection from Tuesday to Thursday.
The Ospreys' 26-cap fly-half Hook, who took a bang to the head in training on Monday, has no full-back experience at the highest level.
We believe we need Hook on the pitch from the start as he is too good a footballer not to be used
Wales coach Warren Gatland
He was a regular at 12 outside Jones in former Wales coach Gareth Jenkins' ill-fated reign, but the combination rarely clicked and was abandoned after the disastrous World Cup campaign, the now-injured Gavin Henson stepping in.
"We know where we were left wanting in the first Test and we have made selections aimed at improving those areas on Saturday," said coach Warren Gatland.
"We know what James Hook can do and we believe we need him on the pitch from the start as he is too good a footballer not to be used.
"He has gone well at full-back in training during some pretty intense sessions and he will be able to play a big part in the game from 15.
"Knowing how physical the South African midfield were last week, Jamie is the biggest back we had on the field so he will give us more 'go forward' in the centre position.
"All three back-row forwards we have chosen have vast experience in the positions they will play on Saturday and we believe it will give us a physical combination capable of improving our performance at the breakdown where we need to improve.
"Rhys Thomas has been working hard in training and his selection is an opportunity for him to step up against the world champions.
"Some of the combinations in this selection are new but we are very well aware of the capabilities of the boys we have chosen and we know what options they offer us.
"This week we have had to build from the disappointment of a bad defeat but our preparation over the last few days has been great and confidence is building again.
"We want to win the respect of our opponents and I am confident we have picked a side capable of earning that respect if they play to their full potential.
"We are playing the world champions on their home ground but this Welsh side is learning and developing with every game.
"As a coaching team and a squad this week we have learnt a lot of lessons about how to build from our first defeat together and that will make us stronger in the long run."
Wales team to face South Africa: James Hook (Ospreys); Mark Jones (Scarlets), Tom Shanklin (Blues), Jamie Roberts (Blues), Shane Williams (Ospreys); Stephen Jones (Scarlets), Gareth Cooper (Gloucester); Gethin Jenkins (Blues), Richard Hibbard (Ospreys), Rhys Thomas (Dragons), Ian Gough (Ospreys), Alun Wyn Jones (Ospreys), Ryan Jones (Ospreys, capt), Jonathan Thomas (Ospreys), Gareth Delve (Gloucester). Replacements: T Rhys Thomas (Blues), Duncan Jones (Ospreys), Ian Evans (Ospreys), Dafydd Jones (Scarlets), Warren Fury (London Irish), Andrew Bishop (Ospreys), Tom James (Blues).
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