Statto: Given wins 110 cap - most capped Irish player ever
Uruguay produced a quality first-half display as they held on to stave off a spirited Republic of Ireland fightback.
Diego Lucano put the visitors ahead early on after the Irish failed to clear Diego Forlan's free-kick as he blasted home from close range.
But if their first was slightly fortuitous, their second and third were sublime. Shane Long, though, punched back for the Irish as he rose the highest to nod home.
Edinson Cavani then produced a quality finish to put the South Americans back in front before Abel Hernandez finished off a rapier counter with aplomb.
Ireland were resilient as ever and immediately after the interval Keith Fahey scored from the penalty spot to give them some hope, but the talented visitors held on to win as Andy Keogh's late effort was ruled out for offside.
Defeat in a friendly against strong opposition was no disgrace and Giovanni Trapattoni will have been delighted at the way his fringe players fought in the face of a stern test.
Having sent his senior men home in the wake of the 2-1 Euro 2012 qualifying victory over Macedonia on Saturday evening, the Italian challenged his squad to show what they could do against opposition of a very different pedigree.
Uruguay, of course, reached the last four in South Africa last summer and, despite their surprise 2-0 friendly defeat in a snowy Estonia on Friday, arrived in Dublin with a formidable reputation.
By contrast, Trapattoni's starting XI boasted a total of just 103 senior caps between them - six fewer than Kevin Kilbane's personal haul, a measure both of their relative inexperience and the full-back's longevity.
But by the time French referee Said Ennjimi brought the first half to a close, the men in green were in little doubt as to what they were up against.
If there was an element for fortune about the South Americans' opening goal, their second and third were well worked and clinically taken.
Uruguay went ahead with just 12 minutes gone when Fahey saw his clearing header come back off Cavani and fall invitingly to the unmarked Lugano, who took full advantage.
But Ireland were level within three minutes when Long rose to power a header from Liam Lawrence past keeper Fernando Muslera, who had earlier somehow fumbled a Fahey shot over his crossbar.
However, it did not take the visitors long to re-establish their superiority.
They warmed to their task as the half wore on with the movement of front three Cavani, Forlan and Hernandez dragging the home defence all over the pitch with the help of midfielder Egidio Arevalo Rios.
Uruguay restored their lead with 22 minutes gone when Maximiliano Pereira cut along the edge of the penalty area before picking out Cavani, who passed the ball into the far corner.
Hernandez, who had got gradually closer with three previous attempts, finally found his range with an equally adept finish five minutes before the break after Alvaro Pereira had picked off Fahey's pass to Lawrence and played him into space.
It took Ireland just three minutes of the second half to drag themselves back into the game after Long once again caused problems.
The striker broke free down the right and evaded Lugano's attentions before cutting the ball back into the path of James McCarthy and Keogh.
Martin Caceres' desperate challenge only succeeded in bringing both men to earth and referee Ennjimi pointed straight to the spot.
Fahey obliged to make it 3-2 and rekindle hope among a sparse home crowd.
Long might have levelled with seven minutes, although he could not control his shot after Muslera parried Keogh's firm strike.
Opposite number Keiren Westwood had to make a smart save from Forlan's swerving 61st-minute free-kick as Uruguay responded, and Darren O'Dea got in an important block six minutes later to prevent Hernandez from converting Maximiliano Pereira's driven cross.
Substitute Keith Treacy forced a decent 69th-minute save from Muslera, but Westwood had to be at his best seconds later to make a double stop from first Cavani and then Hernandez.
Lawrence cleared a Diego Godin header off the line with 14 minutes remaining, but Keogh thought he had snatched a draw five minutes later, only for his header to be ruled out for offside.