Uruguay, the record 15-time Copa America champions, were eliminated in the group phase for the first time since 1997 after slumping to a shock 1-0 loss to Venezuela in Philadelphia yesterday.
That result combined with Mexico's 2-0 Group C win over Jamaica in Pasadena left the 2011 champions struggling to digest a humiliating early exit.
"We never found the game we wanted and that cost us," Uruguay's revered coach Oscar Tabarez said, adding that the ill-fated campaign should serve as a warning to his team as they now look ahead to the resumption of 2018 World Cup qualifiers.
Uruguay's defeat also capped a miserable tournament for Barcelona superstar Luis Suarez.
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Suarez, nursing a hamstring injury when he joined up with the squad, has so far not played a single minute. Suarez appeared in the dugout and looked visibly frustrated at his failure to get on the pitch, at one point appearing to punch the dugout wall.
Tabarez defended his decision not to name Suarez in the squad.
Venezuela's winner came on 36 minutes, when midfielder Alejandro Guerra cleverly spotted Uruguay goalkeeper Fernando Muslera off his line.
Guerra unleashed a long-range effort from near the halfway line which the back-pedalling Muslera could only parry onto the bar before Salomon Rondon bundled in the rebound from close range.
- Beating 'the maestro' -
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"To beat the 'Maestro' Tabarez is a privilege," Venezuela coach Rafael Dudamel said. "For me it means a lot. He's one of the best coaches in the world, in history. This win will motivate us to keep winning and growing as a team," he added.
Mexico, who had beaten Uruguay 3-1 in their opening game, meanwhile proved too powerful for Caribbean minnows Jamaica in front of an 83,263 crowd at the Pasadena Rose Bowl.
With California's large population of Mexican-Americans making it a virtual home for 'El Tri', Mexico took the lead on 18 minutes when former Manchester United and Real Madrid striker Javier Hernandez nodded in his 45th international goal after 18 minutes.
Jamaica were denied what looked like a clear-cut penalty in the second half after striker Clayton Donaldson appeared to have been fouled in the area.
Jamaica's misery was sealed when Mexico's Hirving Lozano picked out Hector Herrera in the area and the midfielder nudged the ball on for substitute Oribe Peralta to stroke the ball first time inside the right hand upright on the 81st minute.