Jonathan Sexton kicked four penalties as the Irish seized the 12-3 interval lead their dominance deserved, only for the Springboks to then ignite their power game.
Ulster scrum-half Ruan Pienaar crossed for the night's only try in the 45th minute and Pat Lambie kicked 11 points as South Africa, who started as strong favourites, took control.
The result condemned Ireland to a fifth successive Test defeat, which is their worst losing run for 14 years as they failed to claim redemption for a painful 60-0 drubbing by New Zealand in June.
Missing the highly-influential Brian O'Driscoll, Paul O'Connell, Rory Best, Stephen Ferris, Sean O'Brien and Rob Kearney to injury, they entered the match unburdened by high expectations.
But despite the absence of six key personnel, they will be disappointed by their inability to dispatch opposition that was lethargic and pedestrian in the first half.
Ireland have won three of their last four meetings with South Africa and Saturday night was a missed opportunity to improve that sequence.
The absence of Lions captains O'Driscoll and O'Connell saw Jamie Heaslip lead the team for the first time and while he sought to inspire his side, he was sin-binned in the second half.
Full-back Simon Zebo, winning his second cap, passed an early test under the high ball and moments later Gordon D'Arcy launched an intelligent counter-attack that ended with a poor chip kick from Keith Earls.
Just 10 minutes into the game and South Africa had conceded four cheap penalties, two of which were sent between the uprights by Sexton.
It was an encouraging start by muscular Ireland, who were having few problems dealing with the Springboks' route one approach.
Earls knocked on just as he was sent through a gap by Sexton and the fly-half then took time to climb to his feet after halting a bulldozing run by JP Pietersen.
Lambie and Sexton exchanged penalties but Ireland were still playing most of the rugby, showing invention as they worked their way downfield.
D'Arcy was thriving in the absence of O'Driscoll as he welcomed the responsibility of being the senior figure in Ireland's midfield.
Repeatedly tested under the high ball, Tommy Bowe had impressed while man of the match Mike McCarthy and the Irish back row of Heaslip, Peter O'Mahony and Chris Henry were making their presence felt.
South Africa's composure crumbled as first Willem Alberts kneed Sexton in the ribs and then Pietersen was sent to the sin bin for using the shoulder while tackling Henry early.
Another three points from Sexton punished the Springboks' indiscipline as Ireland opened a 12-3 lead they fully merited.
The home side's superiority in broken play and out wide was evident, but they also looked happy to mix it with the bigger South African pack.
Sexton missed his first penalty of the evening and the half finished with Springbok scrum-half Pienaar falling short from long range.
McCarthy cut Eben Etzebeth in half with a bone-jarring hit just moments after Cian Healy had wobbled off to be assessed by a specialist in the concussion bin.
But South Africa were finally coming alive and almost crossed through hooker Adriaan Strauss at a line-out drive in a passage of play that saw Heaslip sin-binned for standing offside.
Scenting blood, the Springboks went for the jugular and were rewarded when Pienaar darted over from close range with Lambie converting.
The landscape of the match now look radically different with rejuvenated South Africa just two points behind.
Captain Jean de Villiers bulldozed through D'Arcy and Earls as referee Wayne Barnes offered Lambie another shot at goal which he took.
Ireland responded with a fiery passage of play that ended when Healy, who had passed his concussion test, was penalised for failing to release the ball.
Sexton and Lambie both fell short with a long-range kicks in a pressure-cooker final quarter of the match.
South Africa were now gaining a foothold at the scrum, winning two penalties in quick succession, the second of which Lambie steered between the uprights.
Ireland desperately chased the late score that would nudge them back into the lead, but were strangled out of the game by the canny Springboks.