Pieter-Steff du Toit is missing from the back row for the first of the three games and his place is taken by Franco Mostert. Leicester Tigers No 8 Casper Wiese will join him in the back row along with inspirational skipper Sisya Kolisi.
Departing Sale Sharks scrum half Faf de Klerk will join Elton Jantjies at half-back and there is plenty of fire power in the threequarter line in wings Chelsin Kolbe and Makazole Mapimpi, and centres Lukhanyo Am and Damian de Allende.
“Wales have been training together for a few weeks now and we have no doubt that they will give everything against us on Saturday,” said Nienaber.
“They are an experienced squad and they have top-class players in their ranks, with some of them having represented the British & Irish Lions last year, so we are expecting a hard grind of a Test.
“They have physical forwards and backs that spark something from nothing, so we need to deliver a quality performance in order to get our season off to a strong start.”
Nienaber has picked six forwards and two backs on his bench in a bid to maintain the forward ferocity and intensity expected from a giant Springbok pack.
“We have a talented group of players, and we believe the match-day squad we selected ticks the boxes in terms of what we would like to achieve in the opening Test against Wales,” added Nienaber.
“We have a plan for the season in terms of giving some of the young players a chance to show what they can do at international level, while at the same time taking stock of the seasoned campaigners and where they are in terms of their rugby.
“Unfortunately, with such a big squad there will always be a few unlucky players, but it is a fine balancing act to ensure we win Tests, build squad depth and transform as a team in the way we play.”
There are seven changes to the starting line-up that went down 27-26 against England at Twickenham in the side’s last outing in November last year.
South Africa (v Wales): Damian Willemse; Cheslin Kolbe, Lukhanyo Am, Damian de Allende, Makazole Mapimpi; Elton Jantjies, Faf de Klerk; Ox Nche, Bongi Mbonambi, Frans Malherbe, Eben Etzebeth, Lood de Jager, Siya Kolisi (captain), Franco Mostert, Jasper Wiese
Replacements: Malcolm Marx, Steven Kitshoff, Vincent Koch, Salmaan Moerat, Elrigh Louw, Kwagga Smith, Herschel Jantjies, Willie le Roux