The Springboks, defending their top-four world ranking in the first of three November tests and without a string of first team regulars, trailed 12-3 at the break when Jonathan Sexton kicked the hosts into a commanding lead.
Ireland failed to profit from the visitors losing JP Pietersen to a yellow card before the break but South Africa made no mistake after Jamie Heaslip was sent to the sin bin and a Ruan Pienaar try together with the boot of Pat Lambie saw them home.
The inexperienced hosts, missing first-team regulars Brian O'Driscoll, Rob Kearney, Paul O'Connell, Stephen Ferris, Sean O'Brien and Rory Best, were in total control early on and inched ahead thanks to two Sexton penalties in the opening ten minutes.
South Africa, whose own injury crisis continued into the morning of the game when they lost prop Tendai Mtawarira to a recurrence of mild heart palpitations, cut the lead in half minutes later when Lambie slotted over an easy three points.
They were made pay for giving away their fifth penalty inside the first 20 minutes when Sexton restored the six-point advantage and after Lambie failed with his second shot at goal, Sexton made it four successful kicks from four on the half hour.
The game then swung on the two yellow cards, the first dished out to Pietersen for a shoulder charge on Irish flanker Chris Henry that almost kicked off a 30-man brawl but ultimately saw the Irish fail to take advantage.
South Africa showed how it should be done when the tables were turned early in the second half and Ireland were reduced to 14 men when number eight Heaslip, captaining his country for the first time, was sent to the sin bin for pulling down a maul.
Already deep in opposition territory, the Springboks piled the pressure on and scrumhalf Pienaar, who plays his rugby in Ireland with Ulster, dived over the line for the game's only try. Lambie's conversion trimmed the advantage to two.
By the time Heaslip returned, his side's nine-point lead had become a one point deficit thanks to another Lambie penalty.
Sexton missed a long-range opportunity to get back on top on the hour and Lambie also left a kick short before making it 16-12 after the South African scrum bullied their opposite eight into submission.
Ireland, who handed debuts to two front rowers including South African native Richardt Strauss and fielded four players starting an international for just the second time, never threatened after that and ended a poor second half scoreless.
Declan Kidney's side may now need to defeat Argentina, buoyed by Saturday's comprehensive 26-12 win over Six Nations champions Wales, in two weeks time if they are to stay in the top eight and secure a second-rank seeding.
South Africa, who face Scotland next weekend before taking on England a week later, need a good tour to stay among the leading four ranked sides and ensure a top seeding for the 2015 World Cup when the draw is made next month.