In a double for Aviva Premiership club Harlequins, Robson will follow Chris Robshaw in leading a team out in the second tour match at GWK Park.
The starting line-up is completely changed from the one for the 1st Test in Durban and England Head Coach Stuart Lancaster said: "Every one of the 22 is desperate to play. They have trained superbly and their attitude while waiting for their chance has been first class. There is a lot of competition for places across the board and Wednesday gives these players a chance to lay down a marker and for the whole squad to build some momentum towards Saturday's Test.
"George (Robson) has had a tremendous season for Harlequins, has made a great contribution to this tour already, both in training and as part of the leadership group, and I know he will captain the team well.
"Only Ugo Monye and Alex Corbisiero will not have had any game time by the end of Wednesday but there will still be three matches to go and their opportunity will come."
Nick Abendanon, who joined the England camp this morning to replace the injured Mike Brown, took a full part in training and will be on the replacements' bench.
England (v SA Southern Barbarians, GWK Park, 1500 SA, live on Sky Sports HD)
15 Alex Goode (Saracens)
14 David Strettle (Saracens)
13 Anthony Allen (Leicester Tigers)
12 Jordan Turner-Hall (Harlequins)
11 Christian Wade (London Wasps)
10 Charlie Hodgson (Saracens)
9 Danny Care (Harlequins)
1 Matt Mullan (Worcester Warriors)
2 Joe Gray (Harlequins)
3 Paul Doran Jones (Northampton Saints)
4 Graham Kitchener (Leicester Tigers)
5 George Robson (capt, Harlequins)
6 James Haskell (Otago Highlanders)
7 Carl Fearns (Bath Rugby)
8 Thomas Waldrom (Leicester Tigers)
16 Tom Youngs (Leicester Tigers)
17 Rupert Harden (Gloucester Rugby)
18 Tom Palmer (Stade Francais)
19 Jamie Gibson (London Irish)
20 Lee Dickson (Northampton Saints)
21 George Lowe (Harlequins)
22 Nick Abendanon (Bath Rugby)