England head coach Stuart Lancaster will give Tom Johnson and Joe Marler their England debuts in the first Test against South Africa on Saturday.
Exeter flanker Johnson comes in for the injured Tom Croft, while Harlequins prop Joe Marler, 21, replaces Alex Corbisiero in Durban.
Mike Brown is in at full-back, with Ben Foden moving to the wing in place of the injured David Strettle.
Ben Youngs wins his place back from Lee Dickson at scrum-half.
Lancaster said: "Tom and Joe have had great seasons at their clubs and have worked really hard to get this chance. Both are in great form and have really impressed in training.
"Equally, Mike Brown has been outstanding for Harlequins. By moving Ben to the wing we retain his strike power and aerial skills. We can utilise not only Mike's attacking and defensive assets, but also call on his left-footed kicking game."
With Corbisiero hampered by a knee injury in training this week, Marler is given his chance after an outstanding season with Premiership champions Harlequins, and he admitted it had been a "whirlwind year".
"During the Six Nations, Stuart said 'prepare yourself for your season not ending in May, prepare it for ending in June, so get yourself ready for that'. But until it was announced on 10 May, I didn't really believe it," said the young prop.
Marler added that the experience he gained last season had played a major part in preparing him to step up to international rugby.
"I've always wanted to play for my country at the highest level, but I was pretty immature, riding the first year wave of professional rugby. But after that, I had to knuckle down a bit and look to the future," he said.
Uncapped London Irish centre Jonathan Joseph, who can also play on the wing, is on the replacements' bench alongside Northampton number nine Dickson and fit-again Leicester fly-half Toby Flood, who has been out for the past month with groin and ankle injuries.
Saracens youngster Owen Farrell moves back to fly-half after starting at inside centre in the recent win over the Barbarians.
James Haskell, back in contention for the first time since the World Cup after stints in Japan and sits the game out after only linking up with the squad this week.
South Africa coach Heyneke Meyer has selected three uncapped players in his starting line-up, with first games for the lock pair of Eben Etzebeth and Juandre Kruger, as well as a debut for Sharks flanker Marcell Coetzee.
England: M Brown; C Ashton, M Tuilagi, B Barritt, B Foden; O Farrell, B Youngs; J Marler, D Hartley, D Cole, M Botha, G Parling, T Johnson, C Robshaw (capt), B Morgan.
Replacements: L Mears, P Doran Jones, T Palmer, P Dowson, L Dickson, T Flood, J Joseph.
South Africa: Z Kirchner; 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, C Oosthuizen, F van der Merwe, K Daniel, R Pienaar, P Lambie, W Olivier.