Tom Croft's second score of the match gave the Lions hope of what would have been one of the most memorable victories in more than 120 years of touring before a Mike Phillips try set hearts racing with just five minutes left to play.
The Lions threw everything at a shocked South African side in the closing stages but ultimately it was the world champions who will take a 1-0 lead into next weekend's second Test in Pretoria.
Tries from John Smit and Heinrich Brussow, together with 13 points from the boot of Ruan Pieanaar and three from Francois Steyn eventually proved enough for the hosts as they secured a 26-21 victory in the opening encounter of the three-match series.
The Lions started brightly but, after Stephen Jones had sent a second-minute penalty narrowly wide of the left-hand upright, it was the Boks who were first on the scoreboard.
Francois' Styen's 65-metre clearance took play deep into Lions territory and the tourists found themselves in serious trouble after they lost their first lineout of the afternoon.
A clever chip through then left the Lions in all sorts of difficulties and resulted in a five-metre attacking scrum for the hosts.
Successive waves of attacks from right to left led to skipper Smit powering over from close-range to give his side an early advantage.
As well as pushing the Boks 5-0 in front, Smit's try brought a huge sigh of relief among the South African support. An understandable degree of tension had surrounded the Springbok fans prior to their first meeting with the Lions in 12 years but their captain's early intervention appeared to settle those pre-match nerves.
Pienaar added the simple extras from just five metres to the left of the posts as the Lions were given an immediate reminder of the size of the challenge ahead of them.
The Lions thought they had hit back in spectacular fashion just moments later as Ugo Monye dived over in the left-hand corner. The Quins wing appeared to have supplied a fine finish after taking Brian O'Driscoll's pass 15 metres from the line as the Lions found space on the blindside of a scrum.
Referee Bryce Lawrence was unable to confirm the try so he instead asked television match official Christophe Berdos to give his verdict and, when it finally arrived, it was one that disappointed a passionate Lions support.
Monye was adjudged to have been held up by the outstretched arm of Springbok centre Jean de Villiers meaning the Lions remained seven points behind. To make matters worse, the Boks were awarded a 22-metre drop out rather than having to defend a five-metre scrum.
Instead of being back on level terms or just two points behind, the Lions soon found themselves 13-0 down with a quarter of the match played. A missed penalty attempt from Stephen Jones was sandwiched by successful kicks from Pienaar and Steyn as the Boks showed just how clinical they could be when gaining any sort of footing in the Lions half.
Despite such a disappointing start to their first Test series in four years, Ian McGeechan's men maintained their composure and finally gained some reward for their early ingenuity.
The much-talked about centre partnership of Jamie Roberts and O'Driscoll did the damage, with Croft on hand to provide the telling touch as the Lions registered their first try with 21 minutes on the clock.
Roberts burst straight through the tackles of Adrian Jacobs and debutant starter Brussow after taking a pass from Stephen Jones on the South Africa 10-metre line.
O'Driscoll's supporting angle took him away from the covering Springbok defence, and when he was finally brought down by JP Pietersen, the Ireland captain had the presence of mind to offload to Croft five metres from the Bok line.
This time, referee Lawrence needed no assistance from Berdos as he signalled a well-deserved five points for the Lions.
Stephen Jones had little difficulty with the conversion from 10 metres to the right of the posts and the Lions were back in the game at 13-7 with 21 minutes played.
A second try almost arrived for the Lions just five minutes later but Tommy Bowe was prevented from claiming his fifth score of the tour after Lee Byrne was pulled up for crossing as O'Driscoll drifted across field.
Steyn dragged a long-range penalty wide of the left post as the Lions stayed within a single score but two successive three-pointers from Pienaar saw the Springboks lead 19-7 at the half-time interval.
If the Lions had plenty to do with 40 minutes left on the clock, they had an even greater task facing them with just five minutes of the second period played.
The re-introduction of laws preventing the pulling down of a maul had had been talked about as a possible advantage for Britain and Ireland's elite but it was the South Africans who made the most of the dismissal of one of the game's most-contentious Experimental Law Variations.
Having first won a penalty after driving fully 20 metres, the Boks continued to maul their way forward, with the Lions unable to bring a halt to their momentum. The home side pushed their way over the try line, with Brussow emerging from the bottom of a pile of bodies to further dent the Lions' chances of working their way back into the fixture.
Pienaar continued his impressive form with the boot as his conversion left the Lions chasing a seemingly insurmountable 26-7 deficit with 33 minutes remaining.
Such a margin may have appeared a bridge too far for the Lions but they somehow worked their way back into contention as the Boks made numerous substitutions and took their foot off the pedal seemingly thinking the job was done.
The immense character and pride associated with the world's greatest touring team shone through as the game neared its conclusion, with the Lions dominating their opponents in every single facet of play in the final quarter of an hour.
When Croft sliced through for his second try after 68 minutes the Lions support began to sense something special.
Again Roberts and O'Driscoll were the catalysts for Croft's well-taken score, with the Welshman making yards before his Irish colleague put the Leicester flanker through a sizeable hole five metres from the Bok line.
Stephen Jones kicked the conversion to bring the men in red back to within two scores as the Lions began to believe once more.
Having earlier seen the ball knocked from his grasp as he stretched for the try line, Phillips then pounced from the back of a ruck seven minutes after Croft's score to reignite dreams of victory at the scene of the Lions' heroic second Test triumph back in 1997. The Ospreys and Wales scrum-half dummied to move play wide before darting backing inside for the Lions' third try of the match.
Belief in the Lions' cause was beginning to turn to anticipation and hopeful expectation. Suddenly the Lions were no longer no hopers in Durban. Instead they were gaining the kind of momentum that suggested an outrageous victory might just be on the cards.
A third successful conversion from Stephen Jones closed the gap to just five as the Lions sensed victory against a demoralised South African side clearly on the backfoot.
Unfortunately, five points remained the gap between the sides when Lawrence signalled the end of proceedings after Andries Bekker won a lineout as the hooter sounded and Ricky Januarie cleared to touch.
The Lions had proved their worth but it was the Boks who took the spoils, albeit in a far more uncomfortable manner than they could ever have imagined midway through the second period.
The Lions now know that another defeat is not an option if they intend to leave South Africa with a series victory behind them.
The squad travel to the home of the Super 14 champions the Bulls next Saturday and, despite the outcome of this afternoon's clash, they will arrive in Pretoria full of confidence knowing that, if their performance in the final 20 minutes is anything to go by, they can more than match the Springboks next time out.
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