Munster's Jean de Villiers, Ulster's BJ Botha and Leinster's CJ Van Der Linde are all included for the Millennium Stadium encounter on June 5.
The Boks have traditionally employed a policy of only selecting home-based players in Test squads but that changed last autumn when the same trio were called up during an unsuccessful tour of Europe.
De Villiers, who has been at Munster for just one season but is heading back to South Africa to enhance his World Cup prospects, will start at outside centre, while Botha and van der Linde join skipper John Smit in the front row.
Van der Linde could arrive in the Welsh capital as a Magners League winner, with Leinster set to take on the Ospreys in the Grand Final next weekend.
The giant prop is likely to face a number of opponents from Saturday's final when the Boks travel to Cardiff as Warren Gatland could name a whole host of Ospreys in his Wales 22.
Former Ospreys scrum-half Ricky Januarie is also included, as are French-based stars Frans Steyn and Joe Van Niekirk and Bath's Butch James.
Flanker Francois Louw and South Africa Sevens wing Gio Aplon are the uncapped players in the Bok starting line up which is missing the majority of its first-choice players.
"We have had a few challenges with two of our sides in the Vodacom Super 14 playoffs but we have still been able to assemble a very talented squad," said South Africa head coach Peter de Villiers.
"With only a week to prepare for this Test we are going to structure our training sessions very carefully to make sure that we focus our attentions on the right areas, with defence being one of the most critical.
"There is also the fact that this team has not played together before but we are not looking for excuses, we are accepting the challenge."
South Africa matchday squad to face Wales
Frans Steyn (Racing Metro); Gio Aplon (Stormers), Jean de Villiers (Munster), Butch James (Bath), Odwa Ndungane (Sharks); Ruan Pienaar (Sharks), Ricky Januarie (Stormers); CJ van der Linde (Leinster), John Smit (Sharks, capt), BJ Botha (Ulster), Danie Rossouw (Bulls), Andries Bekker (Stormers), Francois Louw (Stormers), Dewald Potgieter (Bulls), Joe van Niekerk (Toulon)
Replacements: Chiliboy Ralepelle (Bulls), Jannie du Plessis (Sharks), Alistair Hargreaves (Sharks), Ryan Kankowski (Sharks), Meyer Bosman (Cheetahs), Juan de Jongh (Stormers), Bjorn Basson (Cheetahs)
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