Giovanni Trapattoni's deputies gave as good as they got as they ran the World Cup semi-finalists close in Dublin.
A much-changed Ireland looked to be heading for a heavy defeat when they went in at the break trailing 3-1 after witnessing an exhibition of accomplished finishing from the team currently ranked seventh in the world.
Defender Diego Lugano opened the scoring from close range, but after Shane Long had cancelled out his strike with a 15th-minute header, his strikers took over.
Edinson Cavani and Abel Hernandez put the visitors in the driving seat with sumptuous strikes after 22 and 40 minutes respectively, and the writing appeared to be on the wall.
However, Keith Fahey's 48th-minute penalty gave the Irish hope as Trapattoni's players once again demonstrated a refusal to accept their fate, and they almost snatched a draw in the 81st minute but Andy Keogh could only direct his header into the side-netting.
Defeat in a friendly against strong opposition was no disgrace and 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 fringe players 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, Diego 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, before Keogh somehow failed to equalise five minutes later when his header at the far post went into the side-netting.