Centre Jaque Fourie scored two first-half tries in three minutes after flanker Juan Smith rounded off a sweeping move, meaning the game was done and dusted despite Wales flanker Colin Charvis crashing over from close range just before the break.
Charvis' 22nd Test touchdown set a new world record for a forward, beating the previous mark set by Italian lock Carlo Chechinatto, but his personal glory had to play second fiddle.
Wing JP Pietersen and impressive newcomer Ryan Kankowski added further tries for South Africa in front of a 57,000 crowd, with fly-half Andre Pretorius booting three conversions and centre Francois Steyn landing a long-range penalty.
Full-back Morgan Stoddart - Wales' best player on his Test debut - claimed a deserved score, but incoming coach Warren Gatland clearly faces a huge job when he arrives from New Zealand next week.
Wales fell behind in the fourth minute when Steyn slotted a 48-metre penalty which rekindled memories of a similar strike against England at Stade de France in October.
Wales gave as good as they got in the opening exchanges, with centres Gavin Henson and Sonny Parker prominent, and South Africa were unable to establish any momentum.
Referee Chris White did his utmost to let the game flow, and approaching the end of a committed opening quarter, Wales remained in reasonable shape, trailing by just three points.
South Africa undid Welsh optimism in a flash though, cutting them open from their first serious attack.
Pretorious freed Smith in space, and he powered through attempted tackles by fly-half James Hook and wing Mark Jones to claim a slick try.
Pretorius added the conversion, hoisting South Africa 10-0 ahead, but Hook then missed a glorious chance to open Wales' account by rifling wide an easy penalty chance.
The Welsh defence just could not cope as impressive approach work by skipper John Smit and full-back Ruan Pienaar allowed Fourie to cross unopposed.
Pretorius again missed the tricky conversion, but South Africa were not finished, and a third try in 11 minutes left Wales in disarray.
Pretorius' delightful offload freed Pietersen, who put Fourie away for his second touchdown. The fly-half converted, making it 22-0.
Wales though, managed a try of their own before the break when Charvis claimed his touchdown, giving the home fans a glimmer of hope.
But any realistic chance of a Welsh revival were dashed within six minutes of the restart.
Bryan Habana's first run of note split the Welsh defence, and fellow wing Pietersen had the simple task of finishing things off.
Pretorius' conversion made it 29-5, but Wales kept plugging away, their cause being helped when Springboks substitute Albert Van Den Berg was sin-binned just 60 seconds after replacing Bakkies Botha.
And Wales made their one-man advantage count when Hook's crosskick was gathered by Stoddart for a try that Hook improved.
It was resilient stuff by Wales, and a cue for Davies to summon fresh legs, sending on scrum-half Mike Phillips, hooker Rhys Thomas and lock Luke Charteris.
South Africa were rattled by Wales' resistance, although they still had significant breathing space generated by a 17-point advantage.
Kankowski's score finished Wales though, despite South Africa finishing a man short when replacement hooker Bismarck Du Plessis was yellow-carded.