Wales' winless run against the southern hemisphere's 'big three' extended to 17 matches as a clinical South Africa outmuscled the Six Nations champions 24-15 in Cardiff.
First-half tries from Jean De Villiers and Bismarck Du Plessis gave the visitors a commanding 17-6 lead.
But Leigh Halfpenny's third and fourth penalties kept Wales - who lost three players to injury in the first half-hour - in it at half-time.
Halfpenny's fifth penalty made it 15-17 but a third try from Fourie Du Preez with 15 minutes left ended Welsh hopes of only a second ever win over South Africa.
Their last four contests had produced losing margins of five, three and four points before the agonising one-point defeat at the 2011 World Cup.
And despite starting with 10 of the Lions who had contributed to the series victory in Australia over the summer, this was a familiar tale of Welsh woe against the big beasts from south of the Equator.
The hosts started and ended a thunderous opening half brightly, but were undone by two clinical South African tries and the loss of key personnel to injury.
Two of them - wing Liam Williams and centre Jonathan Davies - both departed in the 12th minute after trying to prevent the Springboks' opening try.
Williams took a blow to the head after getting it on the wrong side of a charging Du Plessis's knee, and Davies sustained a shoulder injury in a last-ditch attempt to stop De Villiers on the line.
The loss of Davies, who had already made his presence felt with two sharp breaks in the opening 10 minutes, was particularly damaging.
Wales, notorious slow starters in previous autumn campaigns, had led 6-3 with two early Halfpenny penalties to one from Morne Steyn, the second bringing the prolific Wales full-back his 300th point in Test rugby.
But the Boks took charge in clinical fashion. Opting to counter from deep, they whisked the ball out to Bryan Habana, who arced his way round Wales hooker Richard Hibbard and away from George North before releasing Du Plessis.
The powerful hooker barrelled through the unfortunate Williams and got the ball away to De Villiers, who managed to squeeze over despite the attentions of the remaining Welsh cover.
If that try underlined the Springboks' more enlightened attacking approach under coach Heyneke Meyer, the second, five minutes later, showed off their trademark muscular side.
A powerful line-out maul finished with Du Plessis twisting his way over the line. Steyn added a second conversion before becoming the third player to depart inside the opening quarter, Pat Lambie moving up from full-back with Willie Le Roux joining the fray.
Despite that double whammy, and the sight of tight-head titan Adam Jones limping off on the half-hour, Wales reorganised and rallied before the interval.
Two Halfpenny penalties brought them to within five points to stoke the Millennium Stadium crowd, who were baying for a card when Springboks flanker Francois Louw used first his elbow, then the outside of his fist, to pin Hibbard to the floor.
Referee Alain Rolland settled for a yellow after consultation with the television match official, but Wales were unable to capitalise on their numerical advantage either side of the interval.
The hosts emerged for the second half with Paul James on as their third tight-head prop of the game, having replaced the first replacement Scott Andrews.
Halfpenny's fifth penalty reduced the gap to two points at 15-17 after 55 minutes, before Rolland lost patience with the scrums continually going down and sent Wales loose-head Gethin Jenkins and South Africa tight-head Coenie Oosthuizen, who had only arrived minutes earlier as a replacement, to the sin-bin.
Uncontested scrums ensued for the next 10 minutes, and Wales suffered a major let-off when Springboks prop Tendai Mtawarira knocked on with the tryline beckoning.
But their fortune didn't last as the visitors sealed victory with their third try with 15 minutes left.
Scrum-half Du Preez picked up a loose ball and kicked left-footed into space down the left touchline.
Jaque Fourie appeared to be in front of the kick when he set off in pursuit, but Wales failed to deal with it and the South Africa centre stole in front of Rhys Priestland to flick it into the hands of Du Preez - following up his own kick - to score.
Lambie's conversion took the Boks more than a single score ahead, but even that proved beyond Wales despite some frantic late attacks.
Wales: 15-Leigh Halfpenny, 14-George North, 13-Jonathan Davies, 12-Scott Williams, 11-Liam Williams, 10-Rhys Priestland, 9-Mike Phillips; 1-Gethin Jenkins, 2-Richard Hibbard, 3-Adam Jones, 4-Bradley Davies, 5-Alun Wyn Jones, 6-Dan Lydiate, 7-Sam Warburton (c), 8-Toby Faletau.
Replacements: 16-Ken Owens (for Hibbard, 63), 17-Paul James (for Andrews, 41), 18-Scott Andrews (for A Jones, 30), 19-Luke Charteris (for AW Jones, 72), 20-Justin Tipuric (for Lydiate, 63), 21-Lloyd Williams (for Phillips, 72), 22-James Hook (for Williams, 13), 23-Ashley Beck (for J Davies, 13).
Yellow card: Jenkins (58)
South Africa: 15-Pat Lambie, 14-JP Pietersen, 13-Jaque Fourie, 12-Jean de Villiers, 11-Bryan Habana, 10-Morne Steyn, 9-Fourie du Preez; 1-Tendai Mtawarira, 2-Bismarck du Plessis, 3-Frans Malherbe, 4-Eben Etzebeth, 5-Flip van der Merwe, 6-Francois Louw, 7-Willem Alberts, 8-Duane Vermeulen.
Replacements: 16-Adriaan Strauss (for Du Plessis, 65), 17-Gurthro Steenkamp, 18-Coenie Oosthuizen (for Malherbe, 56), 19-Peter-Steph du Toit (for Etzebeth, 68), 20-Siya Kolisi (for Alberts, 65), 21-Ruan Pienaar (for Du Preez, 77), 22-JJ Engelbrecht, 23-Willie le Roux (for Steyn, 17).
Yellow card: Louw (36-46), Oosthuizen (58)
Referee: Alain Rolland (Ireland)