Toby Flood will replace Owen Farrell at fly-half for England in the second Test against South Africa in Johannesburg.
Jonathan Joseph makes his first Test start in one of five changes to the side that lost the first Test.
Manu Tuilagi switches to inside centre, Ben Foden moves to full-back for the injured Mike Brown, and David Strettle comes on to the left wing.
England were forced to make a change to their original 22 on Friday with Thomas Waldrom taking over from Phil Dowson.
Dowson is suffering from a tight hamstring so uncapped Leicester number eight Waldrom, who scored two tries in a man-of-the-match midweek display against the South Africa Southern Barbarians, could make his Test debut off the bench.
Farrrell drops to the replacements despite landing four penalties and creating a late try for Foden in the first Test, although some of his distribution and decision-making looked jaded.
But despite fielding an untried centre combination, coach Stuart Lancaster denied he has had a "radical" shake-up, as the selection has been portrayed in some quarters.
"If you'd sat down at the end of the World Cup and tried to pick the team that would play against Scotland most people would have said that was a pretty radical selection," he said.
"We have never been afraid to do that if we are confident in the players so, from my point of view, I wouldn't describe it as radical at all.
"Opportunities have been presented due to injury and it gives us a chance to look at different combinations."
Lancaster backed Farrell to make a contribution at Coca-Cola Park (formerly Ellis Park), if introduced as a replacement.
"While people will focus on Owen's dropping, he is on the bench and I am sure he will come on and have a significant role in the game," he added.
"He's had an unbelievable season so he's by no means dropped and forgotten. He's a fantastic player, he's taken the disappointment well, he's trained extremely well and I'm sure he'll be back again."
Flood, who has 48 caps, impressed when he came on as a 54th-minute replacement for the injured Brad Barritt in Durban.
"The time is right [for Flood] to demonstrate his experience and skills," Lancaster said. "Toby has obviously been around England a long time and is one of our most experienced players."
Flood's most recent start came in last year's World Cup against France.
"It's nice to be back in the fold," he said. "It doesn't really get much bigger than Ellis Park in South Africa. I think everyone is chomping at the bit and really looking forward to it."
There are two other changes in the replacements with fit-again prop Alex Corbisiero in for Paul Doran Jones and Alex Goode taking over from Flood.
South Africa have made just the one change to their line-up for Saturday's second game of the three-Test series.
Pat Lambie is recalled at full-back in place of Zane Kirchener, who suffered a knee injury in the first Test.
England: B Foden; C Ashton, J Joseph, M Tuilagi, D Strettle; T Flood, B Youngs; J Marler, D Hartley, D Cole, M Botha, G Parling, T Johnson, C Robshaw (capt), B Morgan.
Replacements: L Mears, A Corbisiero, T Palmer, P Dowson, L Dickson, O Farrell, A Goode.
South Africa: P Lambie; J P Pietersen, J de Villiers (capt), F Steyn, B Habana; M Steyn, D Hougaard; T Mtawarira, B du Plessis, J du Plessis, E Etzebeth, J Kruger, M Coetzee, W Alberts, P Spies.
Replacements: A Strauss, W Kruger, F van der Merwe, K Daniel, R Pienaar, B Basson, W Olivier.