Willie le Roux, the long-time first-choice number 15 for the Springboks, is among the replacements with the versatile Willemse preferred against Scotland, who are likely to take the game to South Africa with ball in hand.
Wingers Kurt-Lee Arendse and Cheslin Kolbe make up a pacey back three, and Damian de Allende and Jesse Kriel are a change to the centre pairing from the side that thumped New Zealand by a record 35-7 in their final warm-up game in London.
Jasper Wiese takes over at number eight from 37-year-old Duane Vermeulen, who drops to the bench, but the rest of the pack remains the same with the only backs among the replacements scrumhalf Grant Williams and Le Roux.
South Africa team:
15-Damian Willemse, 14-Kurt-Lee Arendse, 13-Jesse Kriel, 12-Damian de Allende, 11-Cheslin Kolbe, 10-Manie Libbok, 9-Faf de Klerk, 8-Jasper Wiese, 7-Pieter-Steph du Toit, 6-Siya Kolisi (captain), 5-Franco Mostert, 4-Eben Etzebeth, 3-Frans Malherbe, 2-Malcolm Marx, 1-Steven Kitshoff
Replacements: 16-Bongi Mbonambi, 17-Ox Nche, 18-Trevor Nyakane, 19-RG Snyman, 20-Marco van Staden, 21-Duane Vermeulen, 22-Grant Williams, 23-Willie le Roux.
