But captain Vincent Enyeama said the players had a lot to be proud of, "You are always disappointed when you lose a game, and we are not happy," Enyeama told KickOffNigeria.com.
"But we played a good game. I would say one of our best games in recent years, so I'm proud of the players today."
Diego Lugano put Uruguay in front with a somewhat fortuitous turn-in as the Nigeria defence went to a sleep.
But John Mikel Obi, on his 50th appearance for Nigeria, made the defender look like a discarded part of the furniture as he drew Nigeria level.
The Chelsea man received a Brown Ideye layup, shimmied away from Lugano with a casual drop of the shoulder and placed home with his weaker left foot.
It was a goal of spell-binding skill, ice-cold calm, exquisite technique and measured precision.
But the last word belonged to Diego Forlan, making his 100th appearance for Uruguay.
From nowhere, the Uruguayan striking trinity clicked into gear as Ahmed Musa gave up a turnover, then found himself on his behind in a failed attempt at retrieval.
Luis Suarez found Edinson Cavani, who swept out wide to the arriving Forlan. The former Manchester United man cracked home an unstoppable thunderbolt to Enyeama's top corner.
It proved enough.
Nigeria: Enyeama - Obobona, Echiejile, Ambrose, Omeruo, Ogu (Mba - 66'), Mikel, Ogude, Musa, Brown (Akpala - 73'), Oduamadi (Babatunde - 45')
Uruguay: Muslera - Lugano, Godin, Pereira, Caceres, Rodriguez (Pereira - 87'), Arevalo, Gonzalez, Suarez (Coates - 83'), Forlan, Cavani