Steenkamp is one of six changes to the side which outplayed a World XV last weekend in Cape Town. He replaces Tendai Mtawarira who switches to the bench.
Cornal Hendricks will make his Test debut on Saturday, while his provincial team mate from the Toyota Free State Cheetahs, the uncapped Lood de Jager, has been selected on the bench.
Centre Jan Serfontein earns his first Test start for South Africa, while Fourie du Preez gets the nod ahead of Ruan Pienaar at scrumhalf.
The 32-year-old Steenkamp, who made his international debut on 27 November 2004 against Scotland in Edinburgh, will become the 29th Springbok to reach 50 Test caps. He will also become the sixth prop to achieve this feat behind Os du Randt, CJ van der Linde, Ollie le Roux, Jannie du Plessis and Mtawarira.
“This is a wonderful achievement for Gurthrö and I’m very proud of him,” said Springbok coach Heyneke Meyer.
“He has been playing Test rugby for a decade and is vastly experienced at all levels of the game. Gurthrö always gives everything he has for the Springbok jersey and it’s always good to see commitment and hard work pay off.”
Meyer added that he is expecting a stern challenge from Wales on Saturday.
“They started their tour well with a good win in Port Elizabeth on Tuesday evening and they are always fired up and ready,” said the Springbok coach.
“Wales have an experienced coaching team and they were the Six Nations champions in 2012 and 2013, as well as the back-bone of the British & Irish Lions team which beat Australia last year, so this will be a massive challenge in our first Test of the season.
“Although we got our season off to a good start against the World XV last weekend, there were a few areas of the game we were not satisfied with and which we worked hard on this week. We will have to be at our best on Saturday and we want to make our supporters proud.”
Victor Matfield, who will captain the Springboks for the 18th time in a Test, will equal John Smit’s South African record of 111 Tests in the Green and Gold.
The Springbok team to face Wales in Durban is:
15 Willie le Roux
14Cornal Hendricks
13 JP Pietersen
12 Jan Serfontein
11 Bryan Habana
10. Morné Steyn
9 Fourie du Preez (vice-captain)
8 Duane Vermeulen
7 Willem Alberts
6 Francois Louw
5 Victor Matfield (Captain)
4 Bakkies Botha
3 Jannie du Plessis
2 Bismarck du Plessis (vice-captain
1 Gurthrö Steenkamp
Replacements:
16 Schalk Brits
17 Tendai Mtawarira
18 Coenie Oosthuizen
19 Lood de Jager
20 Schalk Burger
21 Ruan Pienaar
22 Johan Goosen
23 Lwazi Mvovo