The home side last faced the Springboks in the Pool rounds of Rugby World Cup 2015, losing 36-14 at St James' Park in Newcastle, with the 2010 Autumn Tests the most recent home success on a day where stand-off Dan Parks kicked all of Scotland's points to win 21-17.
The return of Glasgow Warriors centre Huw Jones is the only change to the back division.
Lock Jonny Gray return from the bench to start in the second-row, while back-row Ryan Wilson and wing Tommy Seymour - who scored a hat-trick against Fiji - start a third consecutive Test match this autumn.
Start Hogg starts at full-back and at centre Peter Horne is named alongside returning clubmate Jones.
Scrum-half Ali Price is named on the bench, with George Horne not involved this weekend.
Back-row Matt Fagerson has not recoveed sufficiently from the dead leg he sustained against Fiji to feature against South Africa.
Head Coach Gregor Townsend - Assistant Coach at the time of the 2010 win - said: "South Africa have made a lot of improvements over the last three or four months, beating the All Blacks in New Zealand and putting in an 80-minute performance to defeat France in Paris, which underlines their quality.
"Their traditional strength has always been their physicality and this remains a key point of difference for them. We expect them to be confrontational and powerful in their ball carrying, their defence and also at set-piece time. 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.
"We're looking forward to playing one of the best teams in the world and playing once more in front of a sell-out crowd at BT Murrayfield."
Scotland
15 Stuart Hogg VICE CAPTAIN (Glasgow Warriors)
14 Tommy Seymour (Glasgow Warriors)
13 Huw Jones (Glasgow Warriors)
12 Peter Horne (Glasgow Warriors)
11 Sean Maitland (Saracens)
10 Finn Russell (Racing 92)
9 Greig Laidlaw CAPTAIN (Clermont Auvergne)
1 Gordon Reid (London Irish)
2 Stuart McInally VICE CAPTAIN (Edinburgh)
3 Willem Nel (Edinburgh)
4 Ben Toolis (Edinburgh)
5 Jonny Gray (Glasgow Warriors)
6 Sam Skinner (Exeter Chiefs)
7 Hamish Watson (Edinburgh)
8 Ryan Wilson (Glasgow Warriors)
Substitutes
16 Fraser Brown (Glasgow Warriors)
17 Allan Dell (Edinburgh)
18 Simon Berghan (Edinburgh)
19 Josh Strauss (Sales Sharks)
20 Jamie Ritchie (Edinburgh)
21 Ali Price (Glasgow Warriors)
22 Adam Hastings (Glasgow Warriors)
23 Chris Harris (Newcastle Falcons)