Barnes, a finalist on three previous occasions who once described the contest as "posh bingo," finally took the 50,000 pound ($82,000) prize with "The Sense of an Ending," a memory-haunted novel about a 60-something man forced to confront buried truths about his past after the unexpected arrival of a letter.
Former British spy chief-turned-thriller writer Stella Rimington, who chaired the judging panel, said the 150-page novel "spoke to humankind in the 21st century."
She said it was "almost an archetypal book of our time" that examined the unreliability of memory and how little we know ourselves.
"It is exquisitely written, subtly plotted and reveals new depths with each reading," she said.
Barnes, one of Britain's most critically acclaimed novelists, was previously nominated for "Flaubert's Parrot" in 1984, "England, England" in 1998 and "Arthur and George" in 2005. The 65-year-old writer conceded that "in occasional moments of mild paranoia" he had wondered if forces were working against him ever winning.
"I'm as much relieved as I am delighted to receive the 2011 Booker Prize," he said, thanking his publishers "for their wisdom and the sponsors for their check."
Barnes had been the strong favorite to win the award, attracting half of all bets laid through bookmaker William Hill.
He beat five other finalists. Three were British - Stephen Kelman for Pigeon English, A.D. Miller for Snowdrops and Carol Birch for Jamrach's Menagerie. Two Canadian novels rounded out the shortlist: The Sisters Brothers by Patrick deWitt and Half Blood Blues by Esi Edugyan.
One of the English-speaking world's most high-profile literary prizes, the Booker is open to writers from Britain, Ireland and the 54-nation Commonwealth of former British colonies. Founded in 1969, it is officially called the Man Booker Prize after its sponsor, financial services conglomerate Man Group PLC.
It always attracts colorful commentary and controversy, but this year's contest has been particularly combative, with critics accusing the five judges of dumbing-down after Rimington said the finalists had been chosen for readability.
The shortlist drew criticism for excluding some of the year's most critically lauded books, including "On Canaan's Side" by Ireland's Sebastian Barry and "The Stranger's Child" by Britain's Alan Hollinghurst.
And a group of writers, publishers and agents announced it was setting up a rival award that hopes to supplant the Booker as English literature's premier prize.
Literary agent Andrew Kidd, spokesman for the new Literature Prize, said the goal was to create an award "where the single criterion is excellence rather than other factors."
The new prize will be open to any English-language writer whose work has been published in Britain - unlike the Booker, which does not allow American entrants.
On Tuesday, Rimington accused the Booker's critics of patronizing and insulting both authors and judges.
"What's a novel for it it's not to be read?" she said.
She said the judges were pleased that the batch of six finalists was the best-selling in Booker history.
Though only Barnes was an A-list literary name, readers have embraced the novels' pacy plots and varied settings, which range from inner-city London in Pigeon English to Gold Rush-era America in The Sisters Brothers. Jamrach's Menagerie moves from 19th-century London to a whaling ship, while Snowdrops is set in modern-day Moscow and Half Blood Blues in pre-war Paris and Berlin.
"I thought that the intelligence world was the place for intrigue," said Rimington, former director of the MI5 spy agency. "But that was before I met the publishing world."