Jonathan Sexton kicked four penalties as the Irish seized the 12-3 interval lead their dominance deserved, only for the Springboks to 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.
Jamie Heaslip captained Ireland for the first time while Richardt Strauss, who last month qualified for the injury-hit Irish on residency grounds, made his debut at hooker opposite cousin Adriaan, and Simon Zebo won his second cap at full-back.
Springbok prop Tendai Mtawarira withdrew from the team on Saturday morning after suffering heart palpitations and was replaced by CJ van der Linde.
Zebo 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 Jonathan 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.
Pat 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 Brian 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 lock 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 deserved.
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 Ruan 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 Ruan Pienaar darted over from close range with Lambie converting.
By the second half, the landscape of the match looked 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 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.