Brad Shields is set to collect his first England cap from the bench against South Africa on Saturday, but lock Joe Launchbury is not fit enough to make the squad for the first Test.
Former New Zealand youth international Shields qualifies for England through his parents and is in the squad for the first time, having been released from his contract with the All Blacks.
The 27-year-old is now in line to make his debut at Ellis Park, while fellow rookie Ben Spencer is also among the replacements, preferred to Dan Robson.
There is no room for Launchbury, though, who has missed training with a calf injury. Nick Isiekwe is in for a first start.
Mike Brown remains on the wing, with Elliot Daly at full-back. Henry Slade is at 13, as Kyle Sinckler also starts.
There is no room in the 23 for the returning Danny Cipriani, while Alex Lozowski misses out, too.
Owen Farrell will captain the side and head coach Eddie Jones said of his stand-in skipper: "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.
"We want to do something special on this tour and the players are all incredibly excited about this challenge and opportunity we have."
England: Elliot Daly, Jonny May, Henry Slade, Owen Farrell, Mike Brown, George Ford, Ben Youngs; Mako Vunipola, Jamie George, Kyle Sinckler, Maro Itoje, Nick Isiekwe, Chris Robshaw, Tom Curry, Billy Vunipola.
Replacements: Luke Cowan-Dickie, Joe Marler, Harry Williams, Brad Shields, Nathan Hughes, Ben Spencer, Piers Francis, Denny Solomona.