Brexit Party candidates John Longworth, Lucy Elizabeth Harris and Jake Pugh have become MEPs after the announcement at Leeds Town Hall just after 11.30pm yesterday, while Labour's Richard Corbett, the Liberal Democrats' Shaffaq Mohammed and former Sheffield Lord Mayor, the Green Party's Magid Magid, were also voted in.
It means dramatically opposing politicians will be forced to work alongside each other in the European Parliament.
The Brexit Party registered 470,351 votes across the region, the closest contender being the Labour Party with 210,516 - less than half of what the former achieved.
John Longworth, who was the Brexit Party's lead candidate in the region and now MEP, told The Yorkshire Post that the result shows "the good people" of the region have used "their usual common sense".
The Harrogate man said: "They have sent a clear message to Westminster about the way Britain is being handled and also therefore a message about the way we run democracy.
"They're saying 'democracy in Britain is broken'."
He added: "The major parties promised that we would leave in March this year - they reneged on that."
During their time as MEPs, the Brexit Party could "call out" the European Union when it takes decisions which are "not in our best interests", he said.
Following the announcement, Mr Corbett told the audience that the Conservative party's under-performance in the election nationally was "truly historic" and also claimed it was a bad night for the Brexit Party.
Speaking about the latter, he said: "They were probably expecting to get 45 per cent or 40 per cent. They've clearly failed in that objective."
He vowed to back a confirmatory vote on Brexit, and said that denying the electorate another referendum was "tantamount to saying: you had your say three years ago - now shut up and accept whatever the government comes up with".
New Liberal Democrat MEP Shaffaq Mohammed, a youth worker from Sheffield, said: "I will fight for a people's vote to stop Brexit."
He said that the region's diverse communities made him a "proud Yorkshireman".
Magid Magid said: "To Salvini, Farage and Le Pen, I've got a simple message: You have tried to wage war on the hard-fought peace of Europe, But you have shown yourself for who you really are. You are the enemies of every European who swore 'never again'."
He vowed to fight them "every step of the way" and put their politics in the "dustbin of history".
The Somalia-born former Lord Mayor of Sheffield told the Yorkshire Post that contrary to their claims of being anti-establishment, the Brexit Party candidates were the "epitome of the establishment".
He said: "People like myself weren't crafted to go into public office [but we have] provided a real alternative".
Commenting on Donald Trump's planned state visit to the UK next month, he joked: "If it was up to me I'd ban him from the EU. No, Yorkshire and the Humber!"
John Procter, the lead Conservative candidate who failed to win back his seat, said: "Congratulations to those who've won this evening. I hope you enjoy your brief three months in the European Parliament."
Even in some Remain-voting areas such as Leeds and Harrogate, voters backed the Brexit Party over others by substantial large margins.
It won 53,600 votes in Leeds - Yorkshire's largest city - with Labour the nearest party behind with 36,377.
York was the only location to buck the trend regionally, with the Liberal Democrats earning 16,340 votes over the Brexit Party's 15,347.
In Sheffield the Green Party fell behind with 34,803 votes compared to the Brexit Party's 39,534.
The total regional turnout for Yorkshire and the Humber was 1,296,514 - 33.52 per cent of the electorate in the county and a very slight decrease from 2014, when it was 33.63 per cent.
This year it varied from 24.3 per cent in Hull at the lowest, and 42.78 per cent in Harrogate.
The number of MEPs elected is dependent on the population of the region. Yorkshire and the Humber has a population of 5.45million and elects six MEPs.
In 2014, UKIP won 31.3 per cent of the EU election vote and three seats. Labour won two and the Conservatives took the last.
In the 2016 referendum, 58 per cent of the region voted Leave.