British National Party leader Nick Griffin lost his seat as both Labour and UKIP secured three MEPs in the north west region.
Labour topped the poll with 594,063 votes, ahead of second-placed UKIP on 481,932.
The Conservative party, which secured most votes in 2009, was beaten into third place and ended with two seats.
UKIP gained two seats and Labour increased by one.
The Lib Dems’ Chris Davies lost his seat, leaving the party with none.
The new MEPs are Theresa Griffin, Afzal Khan and Julie Ward (Labour), Louise Bours, Paul Nuttall and Steven Woolfe (UKIP) and Jacqueline Foster and Sajjad Karim (Conservatives).
Turnout for the north west was 33.66 per cent.
UKIP’s deputy leader Mr Nuttall, speaking after the declaration, said: “People are rejecting the failed three old parties.
“They have given away something that was never theirs to give away, that’s the sovereignty of our country.
“The age of four-party politics has arrived.”
Labour’s re-elected North West MEP Theresa Griffin said: “I’m proud Labour has topped the poll in the north west region.
“Labour will always be on your side, fighting for jobs and growth.”
Labour MEP Afzal Khan, who was Manchester’s first Asian lord mayor in 2005, said he was “delighted” with his election victory at the expense of the BNP.
He said: “That was my aim, that is what I wanted to achieve. I think he’s got a message of hate and this is a difficult time and we need a message of hope and the people of the North West have given a clear message.
“He’s [Mr Griffin] done nothing for the people of the north west. His whole message was one of hate.”
A poor night for the Liberal Democrats saw the party come in at fifth place in the north west – behind the Green Party, which included Lancaster councillor Gina Dowding.
Seats in the European Parliament are allocated according to the D’Hondt system, a type of proportional representation.
Nationally, UKIP now have 23 seats, an increase of 10.
Labour increased by seven seats to 18, while Conservatives lost seven to now have 18 seats.
The Green party increased by one seat to three, Lib Dems lost nine seats, dropping to just one, and Plaid Cymru have one seat.
UKIP leader Nigel Farage said his party had pulled off “just about the most extraordinary result in British politics for 100 years”.
He said successive encouraging results in local elections gave Ukip a good grounding to win seats in Parliament.
He said: “We have proved in county council elections last year, district council elections this year, that we can win in the first past the post. Perhaps the most significant thing for us in the course of the last few days is we have built up clusters of local council seats and areas and that’s the model the Liberal Democrats used in the 1990s to build up in Parliament.”
Ukip was not the only Eurosceptic party to prosper in the elections, with a series of results across the continent underlining voters’ disillusionment with the political establishment.
One of the most significant winners was France’s far-right Front National party, which was the country’s outright winner with 26 per cent support, some 4.1m votes.