Lawson, the grandson of the late and much-respected Bill McLaren will also take over the scrum-half duties from Edinburgh's Blair.
Ospreys winger Nikki Walker will make his first start for his country since 2008 as he replaces Rory Lamont on the wing.
In the pack, Scott MacLeod, who has shown outstanding improvement for Edinburgh this season and who played a decisive role in Scotland's second Test win in Argentina returns to the starting XV and will partner Richie Gray in the second row.
In the back-row Nathan Hines, who scored a try against the Springboks on their last visit to Murrayfield two years ago, will bring his vast experience to bear from blindside flanker with Kelly Brown moving to No 8 to the exclusion of Richie Vernon.
On the bench, Dougie Hall is preferred to Scott Lawson, his Glasgow Warriors team-mate Moray Low comes in for the injured Alasdair Dickinson and Chris Paterson returns to the Scottish 22.
"We have to show to Scotland's supporters this weekend that we are ready to face up to the intensely physical challenge that the South Africans always present," said Andy Robinson as he announced his side.
"The players are pledged to deliver a much-improved performance this weekend and I believe they can restore pride in the Scotland jersey."
Scotland: Hugo Southwell (Stade Francais), Nikki Walker (Ospreys), Max Evans (Glasgow Warriors), Graeme Morrison (Glasgow Warriors), Sean Lamont (Scarlets), Dan Parks (Cardiff Blues), Rory Lawson (Gloucester) CAPTAIN; Allan Jacobsen (Edinburgh), Ross Ford (Edinburgh), Euan Murray (Northampton Saints), Scott MacLeod (Edinburgh), Richie Gray (Glasgow Warriors), Nathan Hines (Leinster), Kelly Brown (Saracens), John Barclay (Glasgow Warriors)
Replacements: Dougie Hall (Glasgow Warriors), Moray Low (Glasgow Warriors), Richie Vernon (Glasgow Warriors), Ross Rennie (Edinburgh), Greig Laidlaw (Edinburgh), Ruaridh Jackson (Glasgow Warriors), Chris Paterson (Edinburgh)
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