Ireland were left frustrated for the second week running as South Africa clinched a 2-0 series win in Cape Town.
SA: 26 (20)
Tries: Paulse, Fourie
Cons: Montgomery 2
Pens: Montgomery 4
Ireland: 17 (10)
Tries: Howe, O'Driscoll
Cons: O'Gara, Humphreys
Tyrone Howe's early try put the Irish ahead but the Springboks hit back with scores from Breyton Paulse and Jaque Fourie for a 20-10 half-time lead.
Percy Montgomery kicked 16 points on his return to the South Africa side but Brian O'Driscoll's try cut the gap to 23-17 inside the last quarter.
Ireland pressed hard but a first Test win in South Africa remained elusive.
Their brave bid was finally ended when Montgomery knocked over his fourth penalty with the final kick of the match.
The tourists were forced into a late reshuffle due to Geordan Murphy's chest infection, Shane Horgan returning to the wing with Kevin Maggs coming into the centre.
But raking kicks from Ronan O'Gara and O'Driscoll helped the visitors set up camp inside Springboks territory and they opened the scoring in the seventh minute.
Refusing a kickable penalty, Ireland opted for a line-out drive and after Anthony Foley was held up, O'Driscoll's sweet pass put Howe over in the left corner.
O'Gara converted from the touchline to give the visitors a perfect start, but South Africa got themselves on the board with a Montgomery penalty after 16 minutes.
The hosts swept ahead with an excellent try five minutes later, sparked by Montgomery's incisive burst into the line.
O'Driscoll was a constant threat
Ireland conceded a penalty which scrum-half Fourie Du Preez took quickly, and when he was held the ball was moved swiftly left for Paulse to score in the corner.
Montgomery converted and added another penalty to put the 'Boks 13-7 up, O'Gara falling short with a penalty opportunity to cut the deficit.
O'Driscoll continued to inspire his side - releasing Howe with a deft pass before his tackle halted Jaco van der Westhuyzen metres short.
Flanker David Wallace also showed up well but Ireland found themselves a man short after 36 minutes when prop Reggie Corrigan was yellow-carded for a punch on Paulse.
South Africa promptly took advantage as Fourie forced his way over in the right corner, Montgomery converting after being asked to re-take the kick.
O'Gara landed a smart drop goal with the last kick of the half to cut Ireland's deficit to 20-10 at the interval.
The visitors survived some hairy moments on the resumption before Corrigan returned from the sin-bin and a Maggs burst reignited their attack.
Another attempted line-out drive saw lock Paul O'Connell denied a try in the right corner, but Montgomery banged over another penalty to increase South Africa's lead.
Ireland sent on half-backs Guy Easterby and David Humphreys, and the home side were reduced to 14 men when centre Wayne Julies was sin-binned.
The visitors got the break they needed when Humphreys' clever chip bounced kindly for O'Driscoll to touch down, Humphreys' conversion cutting the gap to six points.
But despite a fraught final 15 minutes, South Africa held out and Montgomery had the last word.
South Africa: P Montgomery; B Paulse; M Joubert, W Julies, J Fourie; J van der Westhuyzen, F du Preez; O du Randt, J Smit (capt), E Andrews, Q Davids, V Matfield, S Burger, P Wannenburg, J Cronjeon.
Replacements: H Shimange, CJ van der Linde, G Cronje, G Britz, B Conradie, G du Toit, B Russell.
Ireland: G Dempsey; S Horgan, B O'Driscoll (capt), K Maggs, T Howe; R O'Gara, P Stringer; R Corrigan, S Byrne, J Hayes, M O'Kelly, P O'Connell, S Easterby, D Wallace, A Foley.
Replacements: F Sheahan, M Horan, D O'Callaghan, A Quinlan, D Humphreys, G Easterby, G Duffy.
Referee: Joel Jutge (France)