Ruan Combrinck played a starring role on his international debut as South Africa came from 19-3 down to beat Ireland 32-26 in a thrilling clash at Ellis Park and set up a third-Test decider.
Joe Schmidt's side looked set to follow up last week's historic maiden Test win over the Springboks in South Africa by clinching the series with a match to spare, as their opponents served up an ill-disciplined first-half performance.
However, the introduction of Combrinck helped to turn the tide, the powerful Lions wing scoring one try and playing an integral role in a score for fellow replacement Warren Whiteley as the hosts fought back.
South Africa still trailed by 11 points with 11 minutes remaining, Jamie Heaslip having crossed for Ireland prior to Whiteley's effort, but late tries from Pieter-Steph du Toit and Damien de Allende completed a wonderful Springboks comeback and secured a maiden victory for head coach Allister Coetzee.
16 - Only France (v Wales, 1996) have overturned a bigger HT deficit against a Tier 1 nation than the @Springboks v Ireland (16 pts). Fight.— OptaJonny (@OptaJonny) June 18, 2016
Although an Elton Jantjies penalty gave Coetzee's men an early advantage, Ireland soon had a healthy cushion as Paddy Jackson punished a succession of infringements with accurate kicks.
Jantjies then missed two kicks at goal in quick succession and Ireland took advantage with a fine try towards the end of the first half.
Lwazi Mvovo failed to collect a high kick from Jackson and Andrew Trimble patted the loose ball back for Jared Payne to collect. Full-back Payne was stopped short, but a tremendous offload from Rhys Ruddock enabled Devin Toner to cross, with Jackson adding the extras.
Ireland's fly-half missed tough kicks at goal either side of half-time and South Africa were lifted when a dazzling break from Willie le Roux gave Combrinck the chance to power through Jackson's covering tackle and score in the right corner.
Jantjies converted, but Ireland initially responded magnificently and were 16 points ahead once again when Jamie Heaslip was driven over for a lineout, rewarding the bold decision to turn down a shot at goal.
At that stage, an away win appeared inevitable, but another barnstorming run from Combrinck set the platform for Whiteley to cut in off the left wing and narrow South Africa's arrears.
Du Toit then charged through a tiring defence for his second try in as many weeks and Ireland were left heartbroken when De Allende evaded two attempted tackles to claim the match-clinching score with four minutes remaining.
A Jantjies three-pointer after the hooter rubbed salt in the wounds for Ireland, who must now regroup for next weekend's series decider in Port Elizabeth.