The 22-year-old Stormers front rower is the only uncapped player in Heyneke Meyer’s vastly experienced side for their clash in Cardiff on Saturday.
Malherbe replaces Jannie du Plessis in the Springboks front row after he was ruled out of the tour with a combination of hand and shoulder injuries.
He said: “I actually feel very privileged to play against Wales on my debut, especially in Cardiff at the Millennium Stadium.
“I have never been there, I have watched a lot of Test matches on television and there is an awesome vibe about the place.
“Jannie is a big loss for us, he is veteran of more than 50 tests but I am very honoured to be part of the team.”
Malherbe has been called into the senior South Africa squad twice over the last 12 months but has had to be patient for his debut in the green and gold jersey.
Head coach Meyer said he has “no doubts” the young prop is able to make the grade at international level but he faces a baptism of fire against Wales’ British and Irish Lions trio of Gethin Jenkins, Richard Hibbard and Adam Jones.
Jenkins is set to win his 99th cap for Wales on Saturday.
“He (Jenkins) is obviously a very experienced player but in my side I also have some very experienced guys around me,” said Malherbe.
“Bismarck is one of the best, if not the best, hooker in the world so it’s very good for me to work with him.
“I back myself so I am looking forward to the challenge.
“The set piece will be massively important and if we get that right it will have a big influence on the game. “