Winger Alex Cuthbert scored a memorable try for Wales to cap an exceptional individual performance - but he was left helpless as South Africa snatched second Test glory in the most dramatic fashion.
Blues stars Cuthbert, Gethin Jenkins and Josh Turnbull all started an exhilarating game in Nelspruit while hooker Matthew Rees was a second half replacement.
Tries from former Blues ace Jamie Roberts and Cuthbert put dominant Wales in early control before a penalty try and Cornal Hendricks allowed the Springboks back into the game.
Ken Owens's try extended the lead but Willie Le Roux's effort and a last minute converted penalty try gave the Boks victory.
Meanwhile, there was also a disappointing defeat for new signing Manoa Vosawai as Italy's poor run of form continued against Japan.
Italy's three-Test series in June has failed to produce an upturn in fortunes, with a 25-14 reverse against Fiji followed by a disappointing 15-0 defeat at the hands of Samoa. And the losing streak has now been extended to nine games after a 26-23 defeat in Tokyo.
However, one Blue to taste victory in international rugby over the weekend was lock Filo Paulo who started the game as Samoa defeated Fiji 18-13 in the Pacific Nations Cup clash at the ANZ Stadium in Suva.
The result means both sides finish on six points in the Pacific Conference table of Pacific Nations Cup 2014. Samoa finishes top due to the fact that it beat Fiji and drew with Tonga, Fiji's six points coming from its bonus point win against Tonga and a bonus point for the narrow loss to Samoa.