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."