A heroic defensive effort propelled Ireland to a first-ever win in South Africa by 26-20, despite a red card in the first half to CJ Stander.
Stander's sending off, midway through the opening half, was the big talking point of this match. It came after he knocked Springbok fly-half Pat Lambie out cold while attempting to charge down a chip kick from the pivot.
Referee Mathieu Raynal, after consulting the television match official, Jim Yuille, gave the South African-born back-row his marching orders, although television replays showed that it was a harsh decision with a yellow card probably the right call.
But despite playing with 14 men for most of the match, and even with 13 at one stage, when Robbie Henshaw was yellow-carded late in the same half, Ireland kept their structure, dominated for large periods and held on for a deserved victory.
The Boks looked disjointed throughout and committed a plethora of handling errors and conceded several turnovers, while their decision making also left a lot to be desired.
Ireland's fly-half Paddy Jackson deserves plenty of credit for his game-management in this victory. He was under pressure going into this Test – after getting a place in the starting line-up when first-choice pivot Johnny Sexton withdrew shortly before the tour due to injury – and despite having one of his passes intercepted, from which the Boks scored a try, finished with a 16-point haul via three penalties, two conversions and a drop goal.
The visitors made the brighter start and were on the attack from the kick off when JP Pietersen was penalised for taking Devin Toner out in the air on the edge of the visitors' 22.
Lambie had a chance to open the scoring as early as the fifth minute, however, after Ireland were penalised for an indiscretion at a ruck, but his shot at goal was wide of the target.
Ireland held the upper hand for the next five minutes and although they kept play mostly amongst the forwards they were eventually rewarded when striking out wide with their backs, with Jared Payne crossing for the opening try in the 11th minute when he gathered a Luke Marshall grubber kick behind the Boks' try line.
Jackson added the extras and to add insult to injury for the hosts, Lood de Jager was yellow carded for pulling down a maul in the build-up, after Raynal had penalised the Boks repeatedly for similar offences earlier on.
The Boks eventually opened their account via a Lambie penalty in the 15th minute but Jackson restored parity four minutes later with a three-pointer of his own, from the kicking tee.
Ireland were in the ascendancy, but Stander's red card brought the home side back into the match. Elton Jantjies came on to replace Lambie, who left the field on a stretcher, and shortly after the Lions fly-half's introduction he slotted his side's second penalty.
The home side were soon camped inside their opponents' half for large periods, but Ireland did well to keep them at bay although it was only a matter of time before the Boks would make their numerical advantage count.
And Jantjies would play a leading role in doing just that, setting up Lwazi Mvovo for the Boks' opening try in the 31st minute with a delightful inside pass to the flyer, who showed a tremendous burst of speed which took him clear of the cover defence before diving over.
Ireland suffered a further setback when they were reduced to 13 men after Henshaw was sent to the sin bin for a high tackle on Jantjies in the build-up.
But despite playing with two extra players, South Africa failed to capitalise and it was Ireland who scored the only points during this period with Jackson landing a drop goal in the 36th minute which meant the sides were deadlocked at 13-13 at half-time.
The visitors continued to dominate and from the restart they were soon inside the Boks' 22. And after setting up a couple of phases with their forwards, Conor Murray spotted a gap, before burrowing his way over the try-line.
Jackson's conversion meant the visitors were now leading 20-13 and although the next 20 minutes turned into a slugfest, with no points being scored, the situation suited the visitors.
Jackson gave his side a ten-point lead in the 67th minute when he slotted another penalty but from the restart Pieter-Steph du Toit intercepted a pass from the Irish pivot before scoring under the posts.
Jantjies slotted the conversion and with the score at 20-23, the Boks were back in the match, although time was running out on the clock. They upped the ante on attack but continued to make mistakes and in the 74th minute Jackson added another penalty after Frans Malherbe entered a ruck from the side.
The closing minutes was a frantic affair as the hosts launched several attacks and just before full-time JP Pietersen had a chance to score what could potentially have been the winning try, but he was bundled into touch by three defenders, as Ireland made history.
Man of the Match: Ireland's entire team deserve credit for this result but the performance of captain Rory Best at the coalface of their forward effort should not be underestimated. The hooker led from the front and his decison-making, especially after Stander's sending off, helped pave the way to a memorable and historical Irish victory.
Moment of the Match: One can't look past Stander's red card in the 23rd minute. But although it meant the visitors were reduced to 14 men for most of the match it had the reverse effect on his team-mates who played like men possessed for the rest of the match to secure a memorable result.
Villain of the Match: When scratching the surface, Robbie Henshaw deserves this dubious honour for his ill-timed yellow card, especially considering the fact that his side were already down to 14 men.
The scorers:
For South Africa:
Tries: Mvovo, Du Toit
Cons: Jantjies 2
Pens: Lambie, Jantjies
Yellow Card: De Jager
For Ireland:
Tries: Payne, Murray
Cons: Jackson 2
Pens: Jackson 3
Drop Goal: Jackson
Yellow Card: Henshaw
Red Card: Stander
South Africa: 15 Willie le Roux, 14 JP Pietersen, 13 Lionel Mapoe, 12 Damian de Allende, 11 Lwazi Mvovo, 10 Pat Lambie, 9 Faf de Klerk, 8 Duane Vermeulen, 7 Siya Kolisi, 6 Francois Louw, 5 Lood de Jager, 4 Eben Etzebeth, 3 Frans Malherbe, 2 Adriaan Strauss (c), 1 Beast Mtawarira.
Replacements: 16 Bongi Mbonambi, 17 Trevor Nyakane, 18 Julian Redelinghuys, 19 Pieter-Steph du Toit, 20 Warren Whiteley, 21 Rudy Paige, 22 Elton Jantjies, 23 Jesse Kriel.
Ireland: 15 Jared Payne, 14 Andrew Trimble, 13 Robbie Henshaw, 12 Luke Marshall, 11 Keith Earls, 10 Paddy Jackson, 9 Conor Murray, 8 Jamie Heaslip, 7 Jordi Murphy, 6 CJ Stander, 5 Devin Toner, 4 Iain Henderson, 3 Mike Ross, Rory Best (c), 1 Jack McGrath.
Replacements: 16 Sean Cronin, 17 Finlay Bealham, 18 Tadgh Furlong, 19 Ultan Dillane, 20 Rhys Ruddock, 21 Kieran Marmion, 22 Ian Madigan, 23 Craig Gilroy.
Referee: Mathieu Raynal (France)
Assistant Referees: Angus Gardner (Australia), Matthew Carley (England)
Three penalties apiece from Samoan fly-half Patrick Fa'apale and Georgia full-back Merab Kviriashvili meant that both sides were tied up at 9-9 by half-time.
It was almost a shock result in the first international of this series as the All Blacks continued their run of struggling in their June opener.
Rob Evans' try and two penalties from Dan Biggar handed Wales a 13-10 half-time advantage, despite England crossing twice through Luther Burrell and Anthony Watson.
Outscoring their hosts by three tries to none, England held their nerve when it has let them down so often in the past. The best side in this year's Six Nations now have a Grand Slam to their name.
Four tries from last year's champions built upon 15 points from the boot of Jonathan Sexton as Ireland ensured a tough tournament would end on a high.
Still dissecting their oddly subdued first 50 minutes at Twickenham and trying to put a week spilling over with off-field distractions behind them, Wales started fast and never looked back in an open game where they offloaded perhaps more than throughout all of the four previous games in this year's Six Nations.
Scotland scored three tries, and secured consecutive Six Nations victories for only the third time in history, with a belligerent triumph over France in Edinburgh.
Billed as revenge for their World Cup humbling, perhaps no victory could make up for that disappointment, but instead England delivered what had all the makings of an impressive win before a late surge from Wales left them clinging on.
Ireland's first win of the tournament came all too late with the title set to head elsewhere, but this was a welcome respite after a punishing opening trio of matches.
Two quick tries from Anthony Watson and Mike Brown turned the game in England's favour after Conor Murray had put Ireland ahead following a low-scoring first half.
Tries from back-row duo John Barclay and John Hardie along with a late effort from wing Tommy Seymour saw the Scots come out on top.
George North's comical try in the second-half proved to be the key score as Wales went on to keep an uninspiring French attack at bay.
Leading by just two points at the interval, the pre-game script went to form after the turnaround as England moved through the gears to claim their second victory in as many rounds, with George Ford and Owen Farrell scoring their other tries in what was ultimately an easy win.
The most entertaining game of the 2016 Six Nations to date was far from flawless but Wales kept faith in Warrenball over width to get back to winning ways after that draw in Dublin, before North's solo effort — his first try in six Tests — took the game away from the visitors. Duncan Taylor's consolation score came too late to change the outcome.