Wales' dismal record against the Springboks shows just one win in 29 matches, with their only triumph coming in June 1999.
There have been several close calls in that time - the 6-6 draw in 1970, or one-point defeats in 2011 and June of this year.
But there have also been thrashings - like the 96-13 loss in 1998 - and Wales will be out for revenge in front of what is sure to be a passionate Millennium Stadium crowd in Cardiff.
South Africa have lost just three Tests in a busy 2014 and famously snapped the New Zealand's 22-match unbeaten run with a 27-25 win in October.
A 31-28 victory over England was followed by a 22-6 triumph against Italy and flanker Marcell Coetzee has called for one final effort from his team-mates in Wales, in what he expects to be a physical contest on Saturday.
"I think this will determine our season for this year," Coetzee said.
"We are extremely desperate to win. We know how important it is and the great expectation there is for this game, so we'll just take it as is and come out all guns blazing.
"It will be a big physical battle this weekend."
The Italy win was far from the best Springboks performance and coach Heyneke Meyer has made five changes to his starting side.
Full-back Willie le Roux, wingers Cornal Hendricks and Lwazi Mvovo, prop Tendai Mtawarira and hooker Bismarck du Plessis all come in.
Some of the changes are enforced, though, with JP Pietersen, Bryan Habana and Johan Goosen returning to club rugby.
Wales travelled to South Africa for two Tests in June and lost the opener 38-16, but a strong showing in the next clash - a 31-30 defeat - is sure to give them confidence.
Warren Gatland's side, who finished third in the Six Nations this year, lost to Australia earlier this month before a scrappy 17-13 win over Fiji.
Last week's 34-16 defeat to the All Blacks highlighted the levels that Wales have to aspire to and the hosts had led 16-15 heading into the final 10 minutes.
And lock Jake Ball was keen to take the positives from the experience.
"It's fantastic to test yourself against the best and to think that really we should have won that game," Ball said.
"We should have finished it off and won.
"So it's just showing that we aren't far off and that the game was there for the taking."
Gatland has made three enforced changes, with Liam Williams to replacing the injured George North on the wing, while Gethin Jenkins and Scott Baldwin also come into the side due to the absence of Paul James and Richard Hibbard.