Although Uruguay clinched their 3-0 win with a speculative effort from Diego Forlan, a controversial penalty and a last minute goal, the South Americans were superior in all facets almost from the opening whistle at Loftus Versfeld in Pretoria.
The result ended a 13-match unbeaten run for the hosts, but probably more importantly will serve to deflate the World Cup fever that has engulfed the country.
But hopes of a much improved performance from South Africa, after their 1-1 draw with Mexico in Friday's opener, quickly disappeared under the weight of relentless pressure, both on and off the ball, from Uruguay.
Uruguay coach Oscar Tabarez introduced an extra striker into his starting formation with the inclusion of Edinson Cavani but it was the pairing of Diego Forlan and Luis Suarez which proved decisive.
Their constant probing of the South African back four, mostly at the end of swift counter-attacks, left the home side unable to settle into a rhythm.
South Africa's plan of attacking through the middle with their slick passing game was effectively snuffed out by Uruguay's ability to get men behind the ball as soon as they lost possession. They only had three across the midfield but most times seemed to have a regiment in place.
SUPERB CONDITIONING
South Africa coach Carlos Alberto Parreira said he thought his side were the fittest of the 32 World Cup competitors going into the tournament, but was proved wrong by the superb conditioning of Wednesday's opponents, who seemed to revel in the chilly weather.
Uruguay were almost always first to the loose balls, quick to close down space and swift to see opportunity. Their quick decision-making contrasted with an indecisive approach from the hosts.
South Africa are a team who thrive when their confidence is up but wilt quickly in adversity and they soon dipped their heads, after Forlan's long range drive took a slight deflection and just dipped under the crossbar in the 24th minute.
There was no way back after the penalty awarded some 15 minutes from the end for goalkeeper Itumeleng Khune's trip of Luis Suarez.
The superb balance of Suarez and his darting runs marked a much improved performance after an anonymous showing against France in Cape Town last Friday.
But Forlan was the maestro of the night, reinforcing his reputation among the world's top strikers.
‘Slot hasn’t come in and changed everything, making it all about himself – it’s been about the players he’s inherited, getting the best out of a system he likes’: Liverpool manager impressing former players with personality and tactical approach
‘We thought we’d signed him, but Chelsea blew us away. I think they signed him so we couldn’t have him, as much as because they really wanted him’: Liverpool actually failed to sign Mohamed Salah in 2014, three years before finally getting the Egyptian
