Meyer has followed suit by awarding Frans Malherbe a first cap at tight-head prop following injury to Jannie du Plessis. The Stormers and Western Province youngster has impressed in both Super Rugby and the Currie Cup this term and was heavily tipped to see off the challenge of Lourens Adriaanse for the No3 shirt after Meyer stated that his plan to groom Coenie Oosthuizen as a tight-head was a long-term one.
The other big news among Meyer's selections comes with the inclusion of Japan-based backline stars JP Pietersen and Jaque Fourie. Pietersen is back on the right wing for his first international involvement of the season, while Fourie starts at outside centre having not featured for South Africa since the 2011 Rugby World Cup.
Between them the pair have 117 international caps to their name, with Fourie set for his 70th appearance and Pietersen just two shy of a half century. Both men were key members of the Springbok side that saw off the British & Irish Lions in 2009 and both are highly respected across the globe.
"We're very fortunate to have two world-class players in JP and Jaque available for selection and I wanted to get them into the action as soon as possible," said Meyer. "They bring a vast amount of experience to the team and it was clear from our training sessions thus far that they are in great form and ready for Test rugby.
"Frans has big boots to fill, but he's been with us for most of 2012 and shown good form since recovering from injury recently and we don't have any doubts that he has what it takes to make the step up.
"He'll have two players with more than 50 Test caps each next to him in the scrum (Bismarck du Plessis and Tendai Mtawarira), and his general work-rate across the field and on defence is very good. I'm very happy for Frans."
The only other change to the side that ran the All Blacks close last time out comes in the second row where Flip van der Merwe starts next to Eben Etzebeth. Fellow lock Pieter-Steph du Toit could join Malherbe in making make his Test bow after being named on a replacements' bench that also includes Ulster scrum-half Ruan Pienaar.
"I've been following his career for a long time and Pieter-Steph has always impressed me," added Meyer. "We first invited him to a training camp last year and he probably would've played for South Africa earlier this season had he not got injured. His inclusion in the squad is just reward for a young player who has successfully made the step up to senior rugby.
"To see Frans and Pieter-Steph make the step up to Test match rugby is wonderful. They are two very promising young players and deserve to play for the Springboks, just like we've used - with great success - players such as Willie le Roux, Jan Serfontein, JJ Engelbrecht, Arno Botha, Marcell Coetzee, Siya Kolisi, Eben Etzebeth and Trevor Nyakane in the last two seasons."
Star wing Bryan Habana has recovered from a hamstring injury after four weeks out injured, while Jean de Villiers skippers the side from inside centre and Morné Steyn and Fourie du Preez link up at half back.
South Africa (v Wales, Millennium Stadium, Saturday, 5.30pm)
Pat Lambie, JP Pietersen, Jaque Fourie, Jean de Villiers (captain), Bryan Habana, Morné Steyn, Fourie du Preez; Tendai Mtawarira, Bismarck du Plessis, Frans Malherbe, Eben Etzebeth, Flip van der Merwe, Francois Louw, Willem Alberts, Duane Vermeulen
Replacements: Adriaan Strauss, Gurthrö Steenkamp, Coenie Oosthuizen, Pieter-Steph du Toit, Siya Kolisi, Ruan Pienaar, JJ Engelbrecht, Willie le Roux