Wayne Pivac’s men head to Pretoria looking to swim against the tide of history, having never beaten the Springboks away from home in 10 previous attempts.
They have made more of a habit of beating them in Cardiff in recent years, and came within a last minute penalty try of beating them the last time they headed south of the equator.
Now, on the back of a disappointing Six Nations and a domestic season to forget, Wales are looking to inject some fire into the belly of Welsh rugby once more.
Pivac, who admitted he's struggled to sleep since losing to Italy in March, has named a much changed side to take on the Springboks in the first match of a three test series.
Plenty of change and a first start
Leicester flanker Tommy Reffell will make his debut on Saturday.
Bridgend-born Reffell, who helped the Tigers win this season’s Gallagher Premiership title at Twickenham, will line up in Pretoria alongside back-row colleagues Dan Lydiate and Taulupe Faletau.
Lydiate and centre George North return to international rugby after more than a year away from the Test match arena because of serious knee injuries.
Elsewhere in the pack, Pivac has opted for Will Rowlands and Adam Beard as the second-row partnership. That means 150 cap Alun Wyn Jones is on the bench.
Jones is joined on the bench by fellow Lion Josh Navidi, with Tomos Williams providing scrum-half cover for Kieran Hardy.
A front five that must step up to the greatest of challenges
Much will be made of the omission of Alun Wyn Jones from the second row, but selections in the front row are equally as intriguing.
Wales struggled at scrum time against South Africa last autumn, and it was possibly the one area of the tighest game that swung it in favour of the Springboks.
The hosts’ pack is formidable, as is their bench, and so the eyes of a 50,000 sell out crowd at Loftus Versfeld will be on the first scrum, and every one thereafter.
Gareth Thomas is preferred to Rhys Carre at loose head, while Lion Wyn Jones doesn’t make the 23. Ryan Elias is picked at hooker instead of the very impressive Dewi Lake. While at tighthead, Dillon Lewis starts instead of Tomas Francis, despite Pivac insisting his traditional go to number three is fit.
Pivac insists who comes off the bench will be as important as who starts. What is certain is Wales won’t be able to start on the back foot against a Springbok pack looking to dominate.
Return of the stardust
How Wales compete at the breakdown and set piece will be critical in how they do on Saturday.
However, if they are able to gain parity there, then there is plenty to be excited about in the backline.
George North was a man reborn playing at 13 at the start of Pivac’s reign, only for his rebirth to be stalled by a nasty injury.
He offers so much in the 13 channel, with his size and pace frightening defenders, while also offering a get-out-of-jail card and a useful decoy if those inside him need it.
Then, there’s a certain Louis Rees Zammit. Dropped during the Six Nations, Pivac says he has never come into a Wales camp looking in better shape.
That’s an exciting prospect for Welsh fans. Especially on the dry, quick pitch that Pretoria may well offer up come Saturday.
Who’ll hit the ground running?
Momentum is a funny thing in sport. It can be the wind in your sails that carries you to glory, or it can be taken from you in an instant, leaving you stranded and completely out of sorts.
Wales don’t carry much momentum into this game, having finished in fifth place in this year’s Six Nations and lost to Italy in the final game in Cardiff.
But, with new territory comes new opportunity. Neither Wales nor South Africa have had their squads together for very long.
Pivac says that provides an opportunity come Saturday, describing the preparation for this match as a ‘level playing field’.
Some may argue that isn’t the case, what with South Africa’s clubs having a great season in the United Rugby Championship, while Wales’ were pretty much out of any sort of contention before spring had sprung.
It’s clear this match is viewed as an opportunity for a scalp by Pivac, and he would quite like to catch South Africa cold - or at least a little rusty.
If Wales, who are traditional slow starters, can hit the ground running, then it could be fruitful trip that delivers more than just the chance to safari and play golf. If they don’t, it could be a July of further discontent.
Who will make the most of the occasion?
Loftus Versfeld is a 50,000 sell-out on Saturday. Due to the coronavirus pandemic, it will be the first time South Africa have played in front of full home crowds since they won the World Cup in November 2019.
That is advantage South Africa, undoubtedly, but there’s a chance for Wales to really play up to the underdog tag they have so often enjoyed.
Dan Biggar says the iconic Loftus Versfeld stadium was ‘soulless’ when the Lions played here last summer. He’ll hope it isn’t too raucous come the final whistle on Saturday.
Wales also have their own opportunity to be inspired by those that have gone before.
Come kick off, the players will wear black armbands in honour of former Wales and British and Irish Lions captain Phil Bennett, who died earlier this month.
Benny played some brilliant rugby in South Africa in 1974. There will be no more fitting tribute for a Welsh great than for Wales to banish the demons of history in his honour.
Wales XV to face South Africa: G Thomas, R Elias, D Lewis, W Rowlands, A Beard, D Lydiate, T Reffell, T Faletau, K Hardy, D Biggar, J Adams, N Tompkins, G North, L Rees Zammit, L Williams. Replacements: D LAKE, R Carre, T Francis, A W Jones, Navidi, T Williams, G Anscombe, O Watkin