Launchbury replaces Nick Isiekwe in the second row after recovering from a calf injury while Shields is preferred at blindside flanker to Chris Robshaw, who is dropped for the first time since Eddie Jones took over as head coach.
Shields impressed when introduced from the bench during last Saturday’s 42-39 defeat to the Springboks and will make his full debut in Bloemfontein.
“Based on South Africa’s likely selection of an extra lineout jumper we have decided to start with Brad Shields, which improves our lineout,” said Jones.
“It is tough on Chris Robshaw as he has been an outstanding player for us but I know he will bounce back.”
Robshaw drops out of the matchday 23 with Newcastle’s Mark Wilson named on the bench alongside fly-half Cipriani, who could win his first cap since 2015.
“We are looking for something a little bit different to finish the game, which he can bring,” said Jones of Cipriani.
“He’s been training well and doing everything that has been asked of him.”
England: 15 Elliot Daly, 14 Jonny May, 13 Henry Slade, 12 Owen Farrell, 11 Mike Brown, 10 George Ford, 9 Ben Youngs; 1 Mako Vunipola, 2 Jamie George, 3 Kyle Sinckler, 4 Joe Launchbury, 5 Maro Itoje, 6 Brad Shields, 7 Tom Curry, 8 Billy Vunipola.
Replacements: 16 Luke Cowan-Dickie, 17 Joe Marler, 18 Harry Williams, 19 Mark Wilson, 20 Nathan Hughes, 21 Ben Spencer, 22 Danny Cipriani, 23 Denny Solomona.