Double world champ Smith reaches the landmark after six years, and despite 11 changes to the starting XV, 21 of the Boks' matchday 23 have won a World Cup or two, demonstrating their remarkable strength in depth.
Lock Franco Mostert returns from a broken leg in July and will partner Eben Etzebeth, who captains the side and extends his Springboks caps record to 129. Siya Kolisi is on the replacements' bench.
The Springboks have been overhauled with England at Twickenham in mind next weekend, after winning the Rugby Championship decider against Argentina 48-7 in Mbombela in September.
Coach Rassie Erasmus has opted for a 7-1 bench, with scrum-half Grant Williams the only reserve back.
"This is a seasoned and quality team ... so they know what it takes to perform at this level," Erasmus said on Friday.
"Many of these combinations have also played together this season either during the (July home) series and Rugby Championship, or both, which will be valuable against a quality team such as Scotland.'
New Zealand-born back Tom Jordan will make his first start for Scotland among four changes to the starting XV, as Melbourne's Tuipulotu faces his ultimate challenge as skipper.
The versatile Jordan made his debut as a replacement in the 57-17 win against Fiji last Saturday after qualifying on residency grounds, and is selected at fullback in place of injured Glasgow colleague Kyle Rowe.
Toulouse's Blair Kinghorn, Bath flyhalf Finn Russell Toulon and Toulon scrumhalf Ben White — all of whom were unavailable last weekend as the match was outside the international window — are the three others added to Gregor Townsend's side for the visit of the world champions.
Kinghorn, Scotland's regular fullback, will start on the wing in place of Darcy Graham, who scored four tries against Fiji but dropped out with a head injury. White and Russell take over from last weekend's halves Ali Price and standout Adam Hastings, who both miss out entirely.
The Springboks have won eight consecutive Tests against Scotland since 2012, including 18-3 at the World Cup last year.
Scotland: Tom Jordan, Blair Kinghorn, Huw Jones, Sione Tuipulotu (captain), Duhan van der Merwe, Finn Russell, Ben White; Jack Dempsey, Rory Darge, Matt Fagerson, Scott Cummings, Grant Gilchrist, Zander Fagerson, Ewan Ashman, Pierre Schoeman. Reserves: Dylan Richardson, Rory Sutherland, Elliot Millar Mills, Josh Bayliss, Jamie Ritchie, Jamie Dobie, Stafford McDowell.
South Africa: Willie le Roux, Canan Moodie, Lukhanyo Am, Andre Esterhuizen, Makazole Mapimpi, Handre Pollard, Jaden Hendrikse; Kwagga Smith, Elrigh Louw, Marco van Staden, Franco Mostert, Eben Etzebeth (captain), Thomas du Toit, Bongi Mbonambi, Ox Nche. Reserves: Malcolm Marx, Gerhard Steenekamp, Vincent Koch, RG Snyman, Siya Kolisi, Pieter-Steph du Toit, Jasper Wiese, Grant Williams.
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