The two other changes come in the backs division too - Toby Flood getting the nod ahead of Owen Farrell and Jonathan Joseph making his first start in an England shirt after Brad Barritt lacerated an eyeball in the Durban Test. Fellow 21-year-old Manu Tuilagi steps inside to accommodate the young centre.
On the bench, Saints duo Dickson and Dowson, who both featured in yesterday's comprehensive win over the South African Barbarians, are joined by Alex Corbisiero and Alex Goode - the latter in line to become the fourth England debutant on the tour should he be involved at Coca Cola Park.
Lancaster remains optimistic for Saturday's game despite the unwanted selection troubles.
"I am delighted for JJ," he said. "He has trained very well and showed against the Barbarians and in his short time on the field in the first Test that he is ready to make the step to international rugby. To have two 21-year-old centres is exciting and we are looking forward to seeing this combination in action.
"Owen has had a fantastic season and I am sure he will make a significant impact from the bench. However, Toby has waited patiently for his opportunity and the time is right to allow him the chance to demonstrate his experience and skills in what will be a very tough challenge.
"It's a shame for Mike Brown who worked hard to get that Test start but Ben Foden naturally reverts to full back and we return to the wing partnership of David Strettle and Chris Ashton that serves us well in the RBS 6 Nations."
Springboks boss Heyneke Meyer has made just one enforced change to his starting XV, Pat Lambie stepping in for the injured Zane Kirchner at full back.
ENGLAND SIDE TO FACE SOUTH AFRICA
Coca Cola Park, Johannesburg, SA
Saturday, June 16th, 2012
Kick off: 4pm BST
Live on Sky Sports HD
15 Ben Foden (Northampton Saints)
14 Chris Ashton (Saracens)
13 Jonathan Joseph (London Irish)
12 Manu Tuilagi (Leicester Tigers)
11 David Strettle (Saracens)
10 Toby Flood (Leicester Tigers)
9 Ben Youngs (Leicester Tigers)
1 Joe Marler (Harlequins)
2 Dylan Hartley (Northampton Saints)
3 Dan Cole (Leicester Tigers)
4 Mouritz Botha (Saracens)
5 Geoff Parling (Leicester Tigers)
6 Tom Johnson (Exeter Chiefs)
7 Chris Robshaw (Harlequins) (capt)
8 Ben Morgan (Scarlets)
16 Lee Mears (Bath Rugby)
17 Alex Corbisiero (London Irish)
18 Tom Palmer (Stade Francais)
19 Thomas Waldrom (Leicester Tigers)
20 Lee Dickson (Northampton Saints)
21 Owen Farrell (Saracens)
22 Alex Goode (Saracens)