Despite the huge blow of losing key backs Leigh Halfpenny and Rhys Webb in the run-up to the tournament, nobody in Wales is expecting anything but an emphatic victory for the men in scarlet.
With former world champions England and Australia in the toughest ever World Cup pool, however, Warren Gatland's side cannot afford to treat the encounter just as an opportunity to give squad players a run.
England claimed a bonus point in their 35-11 victory over Fiji in the tournament opener and Wales must at least match that by scoring four tries against the Uruguayans.
With points and try differentials also taken into account when separating teams tied at the end of the pool stage, Wales would be wise to go hard from kickoff and keep the foot on the gas for the full 80 minutes.
Gatland has rested a string of key players ahead of next weekend's crunch match against England in London but has brought Liam Williams and Samson Lee into his side after lengthy spells on the sidelines with injuries.
Williams comes in for Halfpenny at fullback and prop Lee comes into the front row alongside Paul James and hooker Scott Baldwin.
Gareth Davies gets his first start at scrumhalf in place of Webb and will be looking to stake his claim to the number nine short for the remainder of the tournament despite the recall to the squad of British and Irish Lion Mike Phillips.
Openside flanker Justin Tipuric also gets a start in the back row alongside skipper Sam Warburton, who will playing his first World Cup match since being shown a red card in the 2011 semi-final against France.
Uruguay, ranked 19th in world, are embarking on their third World Cup campaign after 1999 and 2003 and looking for an unlikely third victory at rugby's showpiece event.
Coach Pablo Lemoine has called on his mostly amateur players to express themselves but first they will have to come to terms with a febrile atmosphere created by a sell-out crowd under the closed roof at one of the great rugby stadiums of the world.
(Editing by Ed Osmond)
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