Goals from Pedro, Lionel Messi and David Villa secured a deserved victory for the Catalan magicians after England international Wayne Rooney had raised United's hopes with a well-taken first-half equaliser.
The star of an electrifying team performance was Argentinian striker Messi, the 23-year-old maestro whose brilliant effort on 54 minutes saw him equal Ruud van Nistelrooy's record of 12 goals in a single Champions League campaign.
It also took Messi's tally for the season to an astonishing 56 goals in 62 games for club and country, and propelled Barcelona towards their fourth victory in club football's most prestigious competition.
In a poignant finale, the honour of hoisting aloft the famous silver trophy was given to Barcelona's French defender Eric Abidal, playing just two months after undergoing surgery to remove a liver tumour.
"On the day they were a better team," disappointed United defender Rio Ferdinand said afterward as Barcelona celebrated.
"I think they are a great side. They've got a way of playing they all know. Tonight maybe a couple of times we got caught. Give credit where credit's due - they were the better team." Sir Alex Ferguson's United had been determined to avoid a repeat of the 2009 final in Rome, where Pep Guardiola's men had struck early before going on to clinch a 2-0 win at the Stadio Olimpico.
Yet despite a bright opening United were ultimately handed a defeat that was just as emphatic as their loss two years ago, with the Spanish champions revelling in the wide open spaces of Wembley.
United, lining up in an aggressive 4-4-2 formation, had harried Barcelona relentlessly in the early exchanges as they sought to prevent the Catalans from settling into their flowing passing rhythm.
But it was not long before Barcelona found their feet and United were to spend much of the opening half an hour, and the match, firmly on the back foot.
Villa shot wide after being picked out by Messi on the edge of the area and moments later Pedro went close after Xavi and Gerard Pique combined menacingly.
A jinking run by Messi set alarm bells jangling in the Manchester United defence before the striker threaded a lovely pass to Pedro only for United skipper Nemanja Vidic to slide in with an important block.
United had Vidic to thank for another superb piece of defending shortly afterwards, the Serbian judging his tackle brilliantly to deny Messi.
But on 27 minutes, Barcelona's relentless pressure finally reaped its reward. An exquisite pass from Xavi struck with the outside of the boot picked out Pedro and the winger coolly clipped his shot beyond van der Sar.
At that point Ferguson must have been fearing a repeat of Rome.But crucially, United were able to find an equaliser within seven minutes.
