The Red Dragons have been placed in the tournament's toughest group, so an opening-game win is imperative if they are to have any hopes of progressing.
Ever since the draw was made for the World Cup at the end of 2012, the same question has been repeatedly asked: 'Just how did Wales, England and Australia end up in the same pool?'
In simple terms, a poor run of results for the Red Dragons just before the draw was made ensured that they found themselves outside the top-ranked sides worldwide.
Since then, all focus has been on which two of the three heavyweights will make it beyond the group stage and into the knockout rounds.
Home advantage could prove key for Wales, with two of their four fixtures to be played in Cardiff, though the potentially pivotal clash with England next week is to be staged at a sold-out Twickenham.
Before then there is the small matter of overcoming Uruguay, who themselves will be looking to pull off an upset against one of Wales, England or Australia over the coming weeks.
Warren Gatland's side have been struck down by a string of cruel injuries, most recently losing Rhys Webb and kicking machine Leigh Halfpenny in the final warm-up match before the tournament gets underway.
The message from inside the camp is that Wales have the replacements to still compete, but it remains to be seen just how big a blow the loss of Halfpenny in particular will be, as Dan Biggar is instead handed kicking duties.
If the pride and spirit witnessed in 2011 is anything to go by, when the Red Dragons made it to the semi-finals before controversially being knocked out, then it may be they - rather than great rivals England - who are celebrating come October 10.
Recent form: WWWLWW
A nation more famous for its football ability than rugby, Uruguay head to Britain currently ranked at 19th in the world.
Competing at their third World Cup, the South American country had to dig deep to overcome Russia in the playoffs and book their place at the showpiece tournament.
Uruguay have won just two games in their two previous appearances in the competition, beating Spain in 1999 and Georgia in their last sojourn 12 years ago.
Being ranked at 5,000/1 outsiders to go all the way and lift the Webb Ellis Cup says all you need to know about the Teros' long-term hopes, but keeping games tight and picking up a shock win against nervy opponents will be their target.
Realistically, though, it is Fiji who will offer the best hope of a dark horse in Pool A, leaving Uruguay as the potential whipping boys down at the foot of the table.
Coach Pablo Lemoine does bring with him plenty of experience, however, having guided his side to the South America Rugby Championship for the first time in some 33 years.
That is the type of spirit that Uruguay will have to show when they raise to curtain on their campaign at the Millennium Stadium, but against a team desperate for a positive start on home soil, it may be an almighty task in front of them.
Recent form: WLLLLL
The scrum-half knows all about what it takes to achieve stardom, with father Diego widely considered the Teros' finest ever player.
Wales starting lineup:
L.Williams, Cuthbert, Allen, S.Williams, Amos, Priestland, Davies, James, Baldwin, Lee, Ball, Charteris, Warburton, Tipuric, King
Uruguay starting lineup:
Corral, Arboleya, Sagario, Vilaseca, Zerbino, Gaminara, Nieto, Beer, Ormaechea, Berchesi, Silva, Vilaseca, Prada, Gibernau, Mieres
Head To Head
This will actually be the first ever senior meeting between the two sides, having previously avoided each other.
Uruguay's two previous competition appearances ended at the pool stage, while Wales have fared better having made it to the knockout rounds on four separate occasions.
The Red Dragons have competed in all eight World Cups, but their best finish came in the inaugural competition when they finished in third place.
We say: Wales 66-4 Uruguay
All signs point to a heavy winning margin for Wales, despite resting certain key players. Momentum is sure to prove key in Pool A, so a big triumph for the Red Dragons on home soil will do them the world of good ahead of tougher tests to come.