Hartley and Lawes – who left the field against New Zealand with a blow to the head - both successfully completed the graduated return to play protocol and resume for the second Autumn International.
Anthony Watson’s first start on the wing in place of the injured Semesa Rokoduguni is the only alteration for the hosts.
England put up a good fight against the All Blacks in their autumn opener, but ultimately came up short in a 21-24 defeat.
The Springboks had their own woes, however, going down 15-29 to Ireland in Dublin and coach Joe Schmidt has reacted with five changes.
Head coach Lancaster says that any South African XV will be a huge challenge.
"I know the players are looking forward to the challenge," he added. "South Africa have quality and experience across the park and it will be a big test for us."
ENGLAND TEAM TO FACE SOUTH AFRICA
Saturday, November 15th, 2014
Kick off 2:30pm
15 Mike Brown (Harlequins, 30 caps)
13 Brad Barritt (Saracens, 19 caps)
12 Kyle Eastmond (Bath Rugby, 5 caps)
11 Jonny May (Gloucester Rugby, 8 caps)
10 Owen Farrell (Saracens, 26 caps)
9 Danny Care (Harlequins, 49 caps)
1 Joe Marler (Harlequins, 23 caps)
2 Dylan Hartley (Northampton Saints, 58 caps)
4 Dave Attwood (Bath Rugby, 13 caps)
5 Courtney Lawes (Northampton Saints, 33 caps)
6 Tom Wood (Northampton Saints, 31 caps)
8 Billy Vunipola (Saracens, 11 caps)
16 Rob Webber (Bath Rugby, 9 caps)
17 Matt Mullan (Wasps, 6 caps)
18 Kieran Brookes (Newcastle Falcons, 3 caps)
19 George Kruis (Saracens, 1 cap)
20 Ben Morgan (Gloucester Rugby, 24 caps)
21 Ben Youngs (Leicester Tigers, 39 caps)
22 George Ford (Bath Rugby, 3 caps)
23 Marland Yarde (Harlequins, 5 caps)
Replacements: Bismarck du Plessis, Trevor Nyakane, Coenie Oosthuizen, Bakkies Botha, Teboho Mohoje, Francois Hougaard, Handre Pollard, Cornal Hendricks