The 34-year-old lock was surprisingly recalled by the Springboks for their end-of-year tour, just when his international career appeared over after leaving South Africa to join French club Toulon.
He will win his 77th cap as Eben Etzebeth has been demoted to the bench to give the young second-rower a rest. Prop Gurthro Steenkamp and hooker Adriaan Strauss were also brought into the pack in Thursday's team announcement.
In the backs, Willie le Roux takes over at fullback, with Pat Lambie shifting to flyhalf in place of Morne Steyn.
Steyn is on the bench but will have a test on a back injury on Saturday, when the availability of flanker Willem Alberts, who has a shoulder problem, will also be decided.
If Alberts fails his fitness test, Siya Kolisi will be promoted from the replacements.
Winger JP Pietersen will become the 28th Springbok to reach 50 test caps.
"For more than seven years, JP has been one of the most consistent players for the Springboks," South Africa coach Heyneke Meyer said. "He always gives everything he has for his country and this is just reward for the hard work and dedication he's put in over the years."
South Africa started its European tour with a hard-fought 24-15 win over Wales in Cardiff on Saturday.
"We said from the start of the tour that we were going to make a few changes for this test," said Meyer. "We need to keep players fresh and motivated.
"The focus this week has been on further improvement in a number of key areas of the game, most notably our discipline. Last week against Wales we were penalised too much."As anticipated, Meyer made a total of five changes to the starting line-up, while two more are possible because of injury niggles.
In the tight five, Bakkies Botha returns for the first time since the Rugby World Cup in New Zealand in 2011, while Gurthrö Steenkamp and Adriaan Strauss will start at Murrayfield. Eben Etzebeth, Tendai Mtawarira and Bismarck du Plessis are on the bench.
In the backline, Willie le Roux takes over at fullback with Pat Lambie shifting to flyhalf. A final call on the availability of Morné Steyn (back) and Willem Alberts (shoulder) will be made on Saturday.
If Alberts is unfit to start, Siya Kolisi will take his place on the side of the scrum. Marcell Coetzee has been included on the bench in another rotational change with Kolisi, who will sit out if Alberts is passed fit. Steyn has been included on the bench pending a fitness test on Saturday.
“We said from the start of the tour that we were going to make a few changes for this Test,” said Meyer.
“We need to keep players fresh and motivated. Willie and Pat both did well after we lost Morné last weekend and deserve another opportunity on Sunday.
“Gurthrö and Adriaan, who will take over the vice-captaincy as well, have been part of the squad for a long time and will slot in easily. Furthermore, it has been great to have Bakkies back. His enthusiasm has been contagious and the younger guys have already learned a lot from spending time with him.
“We got our tour off to a good start last week against Wales in Cardiff and the focus this week has been on further improvement in a number of key areas of the game, most notably our discipline. In the Castle Lager Rugby Championship, we conceded the fewest penalties, but last week against Wales we were penalised too much. It’s something that is very important to us and we are working very hard on our discipline.”
Stats and facts:
• The Springbok starting team boasts a total of 667 Test caps (412 in the backline and 255 in the forwards), while there are a further 278 caps worth of experience on the bench.
• South Africa and Scotland last met on 15 June 2013 at the Mbombela Stadium in Nelspruit during the Castle Lager Incoming Series. The Springboks outscored Scotland by 30-17 and three tries to two.
• JP Pietersen will be playing in his 50th Test for South Africa. He played 47 of the previous 49 on the wing and two at fullback.
• Jean de Villiers will extend his record as the most-capped Springbok centre, with 79 Tests in this position. He will be the captain for the 23rd consecutive Test, which will put him in fourth place on the list of SA Captains behind John Smit (83), Gary Teichmann (36) and Francois Pienaar (29). Jean and Jaque Fourie will also extend their SA record of 27 Tests as a centre-pairing.
• Bryan Habana will extend his record as the most-capped Springbok wing, with 92 Tests in this position and if he scores a try, will extend his record of 53 Test tries for South Africa.
• If he takes the field, Morné Steyn will extend his record as the most-capped Springbok flyhalf, with 51 Tests in this position. If he scores a try, he will also extend his record of eight Test tries as a flyhalf for South Africa.
• If he takes the field and scores a try Bismarck du Plessis will extend his record of nine Test tries for South Africa as a hooker.
• If he scores a try, Gurthrö Steenkamp will extend his own record of six tries as a prop for South Africa.
• Bakkies Botha last played for South Africa at the 2011 Rugby World Cup in New Zealand against Namibia, on 22 September 2011.
• If Jaque Fourie scores a try he will extend his record of 28 Test tries for South Africa as a centre.
• The referee is Jerôme Garces of France. This will be his second Test involving South Africa – the first was the Castle Lager Rugby Championship match against Australia on 28 September this year at DHL Newlands in Cape Town, which the Springboks won by 28-8.
Springbok Test match records at Murrayfield:
• Most points – 26 (2t, 8c) by Percy Montgomery on 6 December 1997 against Scotland.
• Most tries – two, by six players, the last was by Adriaan Strauss on 17 November 2012 against Scotland.
• Most conversions – eight by Percy Montgomery on 6 December 1997 against Scotland.
• Most penalty goals – four by Morné Steyn on 20 November 2010 against Scotland.
• Most drop goals – three by Jaco van der Westhuyzen 27 November 2004 against Scotland.
15 Sean Maitland, 14 Tommy Seymour, 13 Nick De Luca, 12 Duncan Taylor, 11 Sean Lamont, 10 Ruaridh Jackson, 9 Greig Laidlaw (captain), 8 David Denton, 7 John Barclay, 6 Alasdair Strokosch, 5 Jim Hamilton, 4 Richie Gray, 3 Moray Low, 2 Ross Ford, 1 Alasdair Dickinson
Substitutes: 16 Scott Lawson, 17 Ryan Grant, 18 Geoff Cross, 19 Jonny Gray, 20 John Beattie, 21 Chris Cusiter, 22 Duncan Weir, 23 Max Evans
15 Willie le Roux, 14 JP Pietersen, 13 Jaque Fourie, 12 Jean de Villiers (captain), 11 Bryan Habana, 10 Patrick Lambie, 9 Fourie du Preez, 8 Duane Vermeulen, 7 Willem Alberts/Siya Kolisi, 6 Francois Louw, 5 Flip van der Merwe, 4 Bakkies Botha, 3 Frans Malherbe, 2 Adriaans Strauss, 1 Gurthrö Steenkamp
Substitutes: 16 Bismarck du Plessis, 17 Tendai Mtawarira 18 Coenie Oosthuizen, 19 Eben Etzebeth, 20 Marcell Coetzee, 21 Ruan Pienaar, 22 Morné Steyn/AN Other, 23 JJ Engelbrecht