Youngs replaces Danny Care at scrum-half for his 26th Test appearance and his first start for England alongside his brother Tom, who wins his third cap.
Head coach Stuart Lancaster makes six changes from the team that lost to Australia last weekend. Joe Launchbury comes in for London Wasps team-mate Tom Palmer to make his first Test start alongside Geoff Parling in the second row. Alex Corbisiero (London Irish) takes over from Joe Marler (Harlequins) in the front row alongside Tom Youngs and Dan Cole.
Thomas Waldrom is replaced at No8 by Gloucester’s Ben Morgan, Tom Wood (Northampton Saints) replaces Exeter’s Tom Johnson at flanker and Mike Brown (Harlequins) comes in for Gloucester’s Charlie Sharples on the wing.
There are also call-ups to the bench for the first time in this series for James Haskell (London Wasps), Mouritz Botha (Saracens) and Jonathan Joseph (London Irish).
In all, there are six Leicester Tigers players in the England starting XV. Ben Youngs partners Toby Flood at half-back, Tom Youngs is joined in the pack by Dan Cole and Geoff Parling while Manu Tuilagi continues at centre.
England Head Coach Stuart Lancaster said: “We have picked a team that will give us the best chance of beating South Africa.
"There were some tight calls, which is what you want as coaches, but the players we have brought into start have been training well, will bring a real motivation to make the most of their opportunity and will suit the challenge we face against a tough and physical South African team."
England (v South Africa, 2.30pm Saturday, Twickenham Stadium)
15 Alex Goode (Saracens, 4 caps)
14 Chris Ashton (Saracens, 27 caps)
13 Manusamoa Tuilagi (Leicester Tigers, 15 caps)
12 Brad Barritt (Saracens, 9 caps)
11 Mike Brown (Harlequins, 9 caps)
10 Toby Flood (Leicester Tigers, 52 caps)
9 Ben Youngs (Leicester Tigers, 26 caps)
1 Alex Corbisiero (London Irish, 16 caps)
2 Tom Youngs (Leicester Tigers, 2 cap)
3 Dan Cole (Leicester Tigers, 33 caps)
4 Joe Launchbury (London Wasps, 2 caps)
5 Geoff Parling (Leicester Tigers, 10 caps)
6 Tom Wood (Northampton Saints, 11 caps)
7 Chris Robshaw (Harlequins, capt, 10 caps)
8 Ben Morgan (Gloucester Rugby, 7 caps)
Replacements
16 David Paice (London Irish, 4 caps)
17 David Wilson (Bath Rugby, 21 caps)
18 Mako Vunipola (Saracens, 2 cap)
19 Mouritz Botha (Saracens, 9 caps)
20 James Haskell (London Wasps, 43 caps)
21 Danny Care (Harlequins, 35 caps)
22 Owen Farrell (Saracens, 10 caps)
23 Jonathan Joseph (London Irish, 3 caps)
