There is a first outing in the November internationals for loosehead prop Gordon Reid, while hooker Stuart McInally, locks Jonny Gray and Ben Toolis and flanker Hamish Watson return to the pack.
Gray and McInally had been used off the bench in last Saturday's 54-17 win over Fiji at Murrayfield, but Toolis and Watson were rested after a 21-10 loss to Wales in Cardiff on Nov. 3.
Huw Jones, who played club rugby in Cape Town for four years, is the only change in the backline in place of Alex Dunbar.
Sam Skinner, who was named man of the match for his debut performance against Fiji, moves from lock to blind side flanker in a positional switch as Scotland anticipate a forward battle.
"We expect (South Africa) to be confrontational and powerful in their ball carrying, their defence and also at set-piece time," said Townsend.
"Their traditional strength has always been their physicality and this remains a key point of difference for them. It will be a great challenge for our forward pack in particular.
"South Africa have always had a smart kicking game with an excellent chase but what we've seen over the past few months is an ambition to move the ball from counter attack and a push to get their forwards passing the ball more.
"Our defence will have to be strong to nullify this ambitious attacking game plan," he added.
Team: 15-Stuart Hogg, 14-Tommy Seymour, 13-Huw Jones, 12-Pete Horne, 11-Sean Maitland, 10-Finn Russell, 9-Greig Laidlaw (captain), 8-Ryan Wilson, 7-Hamish Watson, 6-Sam Skinner, 5-Jonny Gray, 4-Ben Toolis, 3-WP Nel, 2-Stuart McInally, 1-Gordon Reid
Replacements: 16-Fraser Brown, 17-Allan Dell, 18-Simon Berghan, 19-Josh Strauss, 20-Jamie Ritchie, 21-Ali Price, 22-Adam Hastings, 23-Chris Harris.
(Reporting by Mark Gleeson; Editing by Christian Radnedge and Jan Harvey)
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