The 66-year-old was named Ultimate Legend at the 15th edition of the annual awards ceremony, one of pop music's biggest nights outside the United States.
"This is the man who invented my job," said U2 Bono, introducing McCartney.
"On the way here Paul McCartney, who was driving the car, was pointing out every place in Liverpool. It was like being in the Pope-mobile with the Pope driving. In the universe of Beatles were the big bang., the
"I saw tonight how much Liverpool means to Paul McCartney and you can feel how much Paul McCartney means to Liverpool."
McCartney was one of several stars on the night to pay tribute to Barack Obama following his victory in the U.S. presidential election this week.
"Many years ago four little boys were born here in Liverpool and we went on to do quite well," McCartney said of his former band the Beatles, the most successful pop act of all time.
"So thanks to all my family, to all of you for coming along to all of you in Liverpool, to everyone in Britain, to everyone in America for voting for Mr. Obama."
The other big winner on the night was Britney Spears, who won the Act of 2008 and categories on a night dominated by U.S. acts.
The prizes marked another step along the comeback trail for the troubled 26-year-old, whose "Blackout" album was well received and will be followed by her new record "Circus" due for release on December 2.
Spears also plans to set the record straight about her highly public meltdown in a 90-minute documentary due to be aired on MTV on November 30.
The singer was not at the packed Echo Arena in northern England, where around 10,000 fans screamed and swayed their way through an action-packed show.
The other multiple winners on the night were U.S. rock band "30 Seconds To Mars," led by actor-turned-musician Jared Leto, who picked up the Rock Out and Best Video awards.
Among the performers were U.S. chart-toppers Beyonce and Kanye West, who won the Ultimate Urban award.
Several acts paid tribute to Obama, whose picture was beamed on a giant screen on stage at the end of a performance of "American Boy" by West and Britain's Estelle.
Arguably the most bizarre award of the night went to British 1980s crooner Rick Astley, whose 1987 single "Never Gonna Give You Up" topped the charts in 16 countries.
He shot back to prominence this year when millions of people were "rickrolled" into playing the song over the Internet when they thought they were clicking on apparently unrelated links.
"2008 Europe Music Awards, you've been rickrolled!" shouted Hollywood gossip columnist Perez Hilton.
Astley beat the likes ofand Spears in the Best Act Ever category.
Other winners included Tokio Hotel, named best headliner of the year, Pink, who won most addictive track for "So What" and Emre Aydin of Turkey who was named Europe's favorite act.
MTV invites fans to decide all but one of the categories -- Video Star -- and in 2007 nearly 80 million votes were cast ahead of the event.