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 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 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."
South Africa have recalled prop Gurthro Steenkamp and centre Juan de Jongh in making two changes.
Steenkamp replaces CJ van der Linde at loosehead after the latter took over as late replacement from Tendai Mtawarira in the 16-12 win over Ireland in Dublin at the weekend.
De Jongh replaces Jaco Taute at outside centre. Both Van der Linde and Taute have been included on the bench.
Steenkamp has not played for South Africa for more than a year.
"It's great to have Gurthro back - we wanted to select him last week but unfortunately he was not 100 per cent fit," coach Heyneke Meyer told the Springboks' official website.
On De Jongh's selection, Meyer added: "My plan has always been to give him a start on this tour as he's been playing very well lately and I'm excited to see what he brings to the team on Saturday."
South Africa were beaten 21-17 by Scotland on their last visit to Murrayfield in 2010 and Meyer predicted a "massive battle" on Saturday.
"We saw the match between Scotland and New Zealand and that the Scots scored three tries against the All Blacks (in a 51-22 defeat) - which is more than any other team has managed against them this year," he said.
"It was their first Test back since their season started and they will not be an easy opponent on Saturday but we've also brushed off some cobwebs in Dublin and have had a good week on the training field."
Saturday's Test will be the 22nd meeting of South Africa and Scotland since the first in 1906. The Springboks have won 16 and lost five.
Scotland team: 15-Stuart Hogg, 14-Sean Lamont, 13-Nick De Luca, 12-Matt Scott, 11-Tim Visser, 10-Greig Laidlaw, 9-Mike Blair, 8-David Denton, 7-Kelly Brown, 6-Alasdair Strokosch, 5-Jim Hamilton, 4-Richie Gray, 3-Euan Murray, 2-Ross Ford, 1-Ryan Grant
Replacements: 16-Dougie Hall, 17-Kyle Traynor, 18-Geoff Cross, 19-Alastair Kellock, 20-John Barclay, 21-Henry Pyrgos, 22-Ruaridh Jackson, 23-Peter Murchie
South Africa team: 15-Zane Kirchner 14-JP Pietersen, 13-Juan de Jongh, 12-Jean de Villiers, 11-Francois Hougaard, 10-Pat Lambie, 9-Ruan Pienaar, 8-Duane Vermeulen, 7-Willem Alberts, 6-Francois Louw, 5-Juandre Kruger, 4-Eben Etzebeth, 3-Jannie du Plessis, 2-Adriaan Strauss, 1-Gurthro Steenkamp
Replacements: 16-Schalk Brits, 17-Heinke van der Merwe, 18-CJ van der Linde, 19-Flip van der Merwe, 20-Marcell Coetzee, 21-Morne Steyn, 22-Jaco Taute, 23-Lwazi Mvovo