Nick Isiekwe will make his first England start in Saturday's first Test against South Africa with Brad Shields named on the bench.
Isiekwe partners Saracens team-mate Maro Itoje in the second row as Joe Launchbury misses out due to a calf problem.
Head coach Eddie Jones has named seven players who featured in last month's Aviva Premiership final in his starting line-up, with Exeter's Henry Slade named alongside captain Owen Farrell in the midfield and Sarries No 8 Billy Vunipola back in an England shirt for the first time since the 2016 Six Nations.
Sale openside Tom Curry wins his second cap, having made his debut against Argentina last June, while Elliot Daly is named at full-back with Mike Brown on the wing.
Hurricanes captain Shields is among the replacements alongside fellow uncapped player Ben Spencer, but there is no place for Danny Cipriani.
"Owen Farrell has settled in well to his new role, with the senior players supporting him, and there is a good feeling within the camp," said Jones.
"We want to do something special on this tour and the players are all incredibly excited about this challenge and opportunity we have.
"Ellis Park is the spiritual homeland of South African rugby and the Springboks play to another level on that ground, so we know we have to raise our game physically early on and be enormously accurate in the way we play."
England are seeking their first series win in South Africa. The Springboks have named three uncapped players in their starting XV for Saturday's first Test in Johannesburg, which is live on Sky Sports Action from 3pm.
England: 15 Elliot Daly, 14 Jonny May, 13 Henry Slade, 12 Owen Farrell (c), 11 Mike Brown, 10 George Ford, 9 Ben Youngs; 1 Mako Vunipola, 2 Jamie George, 3 Kyle Sinckler, 4 Maro Itoje, 5 Nick Isiekwe, 6 Chris Robshaw, 7 Tom Curry, 8 Billy Vunipola.
Replacements: 16 Luke Cowan-Dickie, 17 Joe Marler, 18 Harry Williams, 19 Brad Shields, 20 Nathan Hughes, 21 Ben Spencer, 22 Piers Francis, 23 Denny Solomona.