A second-half goal by Bernard Parker earned South Africa a shock 1-0 win over European and world champions Spain in the same stadium where La Roja won the 2010 World Cup.
The Kaiser Chiefs forward beat Victor Valdes after 57 minutes to stun Vicente del Bosque's side, who produced one of their poorest performances in recent memory to lose only their second match in more than three years.
Controversy reigned in the final quarter of an hour when Valdes became injured after Del Bosque had made all of his substitutions, but Pepe Reina was allowed to come on and replace the Barcelona goalkeeper, despite protests from the South Africa dugout.
Del Bosque fielded a far stronger starting line-up than for the 2-1 win over Equatorial Guinea last Friday, his team featuring seven players who started the World Cup final in 2010.
Yet in spite of their vastly-superior personnel, Spain struggled to impose themselves on their opponents.
They took the initiative from kick-off but, aside from two efforts from David Villa that were ruled out for offside and a wayward shot from Andres Iniesta, did not cause their opponents many problems, despite maintaining 92 per cent possession in the opening 20 minutes.
It was Gordon Igesund's side who fired the first warning shot, Oupa Manyisa thumping the bar after 19 minutes with an effort from outside the area which had deflected off Sergio Ramos.
Spain created their best chance of the half on 27 minutes, Fernando Llorente sending a free header just wide of the post after a ball from Alvaro Arbeloa, and a couple of minutes later La Roja had another goal ruled out for offside, this time Pedro being caught out.
On the stroke of half-time, Bongani Khumalo missed the best chance of the game, glancing a near post header just wide after Parker had swung in a corner.
Just after the re-start, the hosts squandered another glorious chance.
Substitute Siphiwe Tshabalala released Tokelo Rantie, who ran towards goal unchallenged but got too much power on his shot, which went narrowly over the bar.
Nacho Monreal should have done better for Spain when a through ball from Iniesta allowed him to go face to face with Itumeleng Khune, but the Arsenal full-back could only shoot at the goalkeeper's legs.
Then came the goal South Africa deserved.
Full-back Thabo Matlaba got down the left wing and cut the ball back to Kamohelo Mokotjo, who split the Spain defence with a one-touch pass, and Parker lifted the ball over Valdes' outstretched hand and into the far corner.
Spain's response to going behind was to bring on Alvaro Negredo for Villa. The Manchester City forward had a positive impact but was unable to take either of the two chances that fell to him, the first a distance shot which flew over the bar, the second a soft attempt from inside the area which allowed Khune to save.
With 15 minutes remaining, Del Bosque made his fifth and final substitution, withdrawing Iniesta for Koke.
But barely a minute later Valdes, who had replaced Casillas at half-time, fell to the floor in pain with an apparent calf injury.
Arbeloa briefly went in goal, but then referee Osiase Koto gave Spain the green light to make another substitution, with Reina coming on for Arbeloa, to the fury of South Africa coach Igesund.
The Napoli goalkeeper was called into action immediately, denying Rantie when the striker was clean through.
With time running out, Spain struggled to create a clear attempt on goal.
A minute and a half into injury time Cazorla caught sight of goal from 25 yards out but Khune was able to catch the attempt comfortably.
And the goalkeeper came to his side's rescue again with a minute left of the game, pushing away a close-range effort from Albiol.