Cory Allen scored a hat-trick as Wales opened a 28-9 half-time lead.
But the centre may miss the rest of the World Cup with full-back Liam Williams and props Paul James and Samson Lee among other injury worries.
Uruguay fly-half Felipe Berchesi impressed and kicked Los Teros into an early 6-0 lead, before Wales responded.
However, six days before facing England at Twickenham, Warren Gatland's team were not convincing, despite completely dominating the forward exchanges.
Relive Wales' win as it happened.
Wales lacked composure behind the scrum, while Uruguay were dogged and courageous opponents who refused to capitulate even after Wales reached the 40-point mark on the hour.
Wales eventually made their forward dominance pay, with two tries for scrum-half Gareth Davies and one each for Lee, Justin Tipuric and Hallam Amos.
With Jonathan Davies, Rhys Webb and Leigh Halfpenny already out of the tournament, the last thing Wales needed was more injury trouble.
So the sight of full-back Williams limping off with a thigh injury after 35 minutes on his return after foot surgery was a major worry for Gatland, who said it was too early to tell how serious the full-back's injury was.
Gatland also described Allen's hamstring injury as "significant", and he said props Lee and James have calf injuries. Gatland faces a decision over which prop to replace and there is also concern over fellow prop Aaron Jarvis, who has a rib problem.
There was some good news for Wales with flanker Dan Lydiate passing his concussion protocol.
With fly-half Berchesi a lively playmaker and their defence determined to cut down anything in a red shirt, Uruguay started with purpose and were 6-0 up in nine minutes.
Wales hit back with their pack dominating and Lee touching down from a driving line-out.
It was a recipe which troubled the South Americans all afternoon, though the Welsh backs play was less impressive.
But it was Allen who profited most, taking advantage of Rhys Priestland's chip to score the first of his three tries.
His third, on the stroke of half-time, was the pick with Tipuric and Amos combining superbly as Wales claimed their bonus point.
Wales' driving line-out was their main weapon, but this was not a vintage display. Uruguay's mix of full-time Europe-based professionals and home-grown part-timers deserved their lap of honour and the warm applause.
England's pack is unlikely to be as accommodating at Twickenham on Saturday.
Wales coach Warren Gatland: "Hopefully some of those players will recover over the next couple of days. The next day we're back in training is Wednesday to get ready for Saturday.
"The number of turnovers was a bit disappointing. We had 24 turnovers. Respecting the ball and keeping the ball in hand is a big thing.
"I was pleased up front. We stuck to the task and I was pretty happy with some of the performances.
"Tipuric was outstanding again. Jake Ball had a really strong game for us and the front five stuck to their task as well."
Wales captain Sam Warburton: "They were going to be extremely passionate. It was just weathering that storm in the first 10 minutes, being accurate and being as patient as we could.
"I'm a little bit disappointed we didn't look after the ball well enough so there's a lot we can improve on.
"But the main thing was winning and getting a bonus point and we managed to do that.
"The most important thing in this group is picking up your bonus points.
"It's unlikely to come to a [match] points decision."
Wales: Liam Williams (Scarlets); Alex Cuthbert (Cardiff Blues), Cory Allen (Cardiff Blues), Scott Williams (Scarlets), Hallam Amos (Newport Gwent Dragons); Rhys Priestland (Bath Rugby), Gareth Davies (Scarlets); Paul James (Ospreys), Scott Baldwin (Ospreys), Samson Lee (Scarlets), Jake Ball (Scarlets), Luke Charteris (Racing 92), Sam Warburton (capt, Cardiff Blues), Justin Tipuric (Ospreys), James King (Ospreys).
Replacements: Owens for Baldwin (62), Jarvis for James (31), Francis for Lee (40), Day for Charteris (46), Lydiate for Warburton (58), Moriarty for King (46), Lloyd Williams for Allen (54), Morgan for Liam Williams (35).
Uruguay: Gaston Mieres; Santiago Gibernau, Joaquin Prada, Andres Vilaseca, Rodrigo Silva; Felipe Berchesi, Agustin Ormaechea; Alejo Corral, Carlos Arboleya, Mario Sagario, Santiago Vilaseca (capt), Jorge Zerbino, Juan Manuel Gaminara, Alejandro Nieto, Matias Beer.
Replacements: Kessler for Sarazola (77), Duran for Sagario (71), Sanguinetti for Corral (77), Lamanna for Zerbino (61), Alonso for Vilaseca (74), De Freitas for Beer (58), Duran for Ormaechea (74), Bulanti for Prada (74).
Wales claimed a bonus point as they opened their World Cup campaign with a stuttering eight-try win over battling Uruguay at the Millennium Stadium.