Murray, who missed Sunday's 51-22 loss to New Zealand for religious reasons, replaces Geoff Cross in the starting XV.
The second change is enforced, with Ross Rennie (dislocated shoulder) replaced by David Denton.
Denton's inclusion at number eight means captain Kelly Brown will switch to openside flanker.
Murray, who is on loan at Agen from Newcastle and due to join Worcester shortly, last featured on the successful summer tour to Australia, Fiji and Samoa.
The 32-year-old impressed sufficiently to return at the expense of Cross, who scored his first Test try against the All Blacks.
Scotland head coach Andy Robinson said: "I was pleased with Euan's contribution both at scrummage and in open play during the summer tour, while David Denton's aggressive carrying is something that really gets the crowd going."
Scotland must win the match, repeating the 21-17 victory over the Springboks of two years' ago to have any hope of finishing the month in the world's top eight and thus claiming a favourable seeding for the December 3 2015 World Cup draw.
"We know we're in for a bruising battle against South Africa this weekend and we will be primed for that physical confrontation," Robinson added.
"But we also have to be smart in how we approach this game and do our utmost to ensure we get on the front foot and get the result that will move us into the top eight in the IRB world rankings ahead of next month's 2015 Rugby World Cup draw."
On the bench, hooker Dougie Hall, whose most recent cap was in the Rugby World Cup pool match against Argentina in Wellington last year, is preferred to Scott Lawson.
Cross drops to the bench in place of Allan Jacobsen, who is unavailable for personal reasons.
John Barclay returns to the matchday squad and his Glasgow Warriors team-mate Peter Murchie replaces Max Evans and could win his first cap.
Robinson added: "Dougie Hall has had a good season for Glasgow and I know that John Barclay has been one of our most consistent and reliable back-row forwards since he made his debut five years ago.
"Peter Murchie is another who has had a fine start to the season with Glasgow and his desire to dominate in aerial combat has been a factor in selection."
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The entire All Blacks apparel line has been updated for 2013/14. Check out the New Zealand All Blacks polo.
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