Tottenham repelled a second-half onslaught as Andre Villas-Boas masterminded its first away win over Manchester United since 1989.
However, Clint Dempsey scored in between efforts from Nani and Shinji Kagawa to keep Spurs in front, and after Wayne Rooney and Michael Carrick had struck the frame of Brad Friedel's goal, Tottenham clung on for the final whistle.
After the match, United boss Sir Alex Ferguson called for time keeping to be taken out of the control of referees after complaining about the amount added on.
"It is a flaw in the game that referees are responsible for time-keeping," he told BBC Sport. "It is nearly 2013 and the referee still has control of that. They gave four minutes. It is an insult. It is ridiculous. It is denying you the proper chance to win the football match.
The Scot was furious at what he believed was a lack of injury time, which he felt did not take into account six substitions and some time-wasting tactics from the visitors.
"There were six substitutions and the trainer came on. That is four minutes right away," Ferguson said. "The goalkeeper must have wasted two minutes. They took their time at every goal kick. That is obvious to everyone."
The result ended one of English football's longest winless streaks, as well as raising more questions over United's ability to regain the Barclays Premier League title as it slipped four points behind leaders Chelsea.
"We wrote history for our team. The satisfaction comes from that," Villas-Boas said. "The players really felt they could nick a win here and the overall performance was an expression of that desire and ambition, though in different ways. In the first half, we attacked and kept the ball. In the second, we defended."
Tottenham has flattered to deceive in this fixture down the years, so much so that at no point did its two-goal cushion look secure.
Tottenham has even held a two-goal lead at halftime, as it did Saturday, and got swept away by a second-half deluge. On that occasion, in 2009, United had Cristiano Ronaldo leading the thrilling comeback.
There was to be no such drama on this occasion, and Ferguson may be left to reflect on a lack of physical presence in his midfield, which more than anything else was an area ruthlessly exposed by a rampant Tottenham.
There were only two minutes on the clock when Vertonghen strode between Nani and Carrick, drove into the United box and found the corner of Anders Lindegaard's net.
The Belgian's shot did take a significant deflection off Jonny Evans, but Vertonghen deserved his slice of good fortune for the adventure he had shown to take himself into a scoring position in the first place.
"We lost the first goal by not defending properly," said Ferguson. "They got a lucky break when the ball came off Jonny Evans, nonetheless, you can't allow the left back to get as far as that. It was a poor start and from then on, we were against the wind until halftime came along and we were able change things a bit."
Rather than sting United into action, the early goal merely encouraged their visitors.
Bale took up the baton from his teammate and duly sped past Ferdinand and into the box before beating Lindegaard rather too easily to make it 2-0.
Having resisted the temptation to name Rooney alongside van Persie for the first time, Ferguson could delay the inevitable no longer and brought on the England man for Ryan Giggs at the break.
The move triggered a burst of three goals in four minutes, during which any semblance of a game plan for either side was completely ripped up.
Given the history of this fixture, it was no real wonder United should get two of them.
Rooney provided the assist for Nani's close-range effort, curling a low cross to the near post that invited the clinical finish.
Van Persie could claim the credit for United's second as he threaded a precise pass through the Tottenham defense that allowed Kagawa to beat Friedel.
Crucially, though, Tottenham struck its third goal in between United's brace, Bale once again exposing poor defending as he surged forward, and when Lindegaard was unable to hold the Welshman's low shot, Dempsey was on hand to slot home the rebound.
"I've been frustrated," Dempsey told ESPN. "I had one called back against Lazio and then as the games go on, you're not scoring, you start feeling the pressure. But it's good to open my account and it's good for us to get my first win here."
In Rooney, though, United retained that old slugger's instinct.
The striker thudded a brilliant free-kick against a post before van Persie's dismal attempt to finish off a Carrick pass suggested again that it might not be United's day.
It was credit to Tottenham that it managed to clear heads quickly enough to stand firm against the incessant wave of attacks that continued to come.
William Gallas clattered into a post such was his determination to keep Nani's far-post cross away from Rooney, then Friedel turned away a Scholes thunderbolt.
Carrick's header almost sneaked in but dropped against the angle of post and bar instead.
United continued to surge forward, but the equalizer would not come.
And the sight of Evans hobbling off was an unhappy postscript given the defensive problems Ferguson has already encountered.
"We were brilliant in the second half, really unlucky, hit the post, hit the bar, balls scrambled clear. We just dominated it," Ferguson said. "It was a fantastic performance. Thank goodness I am able to say that after watching the first half."
In the aftermath of such a momentous performance, Villas-Boas refused to talk of his team as potential league champions, something Spurs have not achieved since 1961.
"I don't think so," he said. "A couple of days ago, we were exactly the opposite. This is a very special night for us but our quest is to qualify for the Champions League. It is very difficult to go for the title. We understand it is a place where the great teams of this country belong.
"We want to win a trophy this season -- and we want Champions League qualification."
Information from Press Association was used in this report.