In this tournament's 80-year history, surely there has never been such agony for a country, and a continent.
Luis Suarez had used his hands to keep out a header in the last minute of extra time but his red card will be no solace to the Black Stars after Asamoah Gyan's subsequent spot-kick hit the bar and Uruguay ultimately triumphed in the shoot-out.
Ghana players collapsed in tears while Uruguay celebrated their first semi-final appearance, in which they will play Holland, for 40 years.
The South Americans' goalkeeper Fernando Muslera was the hero, saving twice from John Mensah, the Sunderland centre-back, and Dominic Adiyiah, but there was a nasty taste left in the mouth as Suarez was carried shoulder high by his team.
This had been a thrilling, exhilarating, and no-holds barred contest full of thunderous tackles and fierce commitment that really set this World Cup alight.
Sulley Muntari, almost sent home earlier in the tournament after a bust-up with Ghana's Serbian coach Milovan Rajevac, had given his side the lead before Diego Forlan equalised with a viciously-swerving free-kick for his third goal of the finals.
Ghana carried the hopes of the continent with them, and especially South Africans, in their quest to become the first African country to qualify for the semi-finals.
The South Americans, aiming for their first appearance in the last four since 1970, had only conceded one goal all tournament.
Perhaps it was the burden of expectation, but Ghana looked nervous from the start while Uruguay, and Suarez in particular, emanated menace.
Ghana had done virtually nothing when, inspired by Kevin-Prince Boateng, they suddenly began to play.
Muntari struck in first-half stoppage time. The Inter Milan midfielder hit a speculative shot from 30 yards out, Gyan ducked and Muslera was caught flat-footed as the ball sneaked in.
Forlan equalised 10 minutes into the second half with an absolutely outstanding free-kick, the ball swerving one way and then the other on its way in.