Boris Johnson has said he will campaign for the UK to leave the EU as battle lines were drawn between Northern Ireland's politicians on what David Cameron has called one of the biggest decisions of our time.
Dismissing the Prime Minister's reform deal as insignificant, Mr Johnson said he could not turn down this "once in a lifetime" chance to quit the EU.
He claimed Mr Cameron's renegotiation had failed to deliver fundamental change in Britain's relationship with Brussels.
It is a huge boost to the 'Out' campaign, which has already secured the backing of Northern Ireland Secretary Theresa Villiers and First Minister Arlene Foster.
Mrs Foster said there was "nothing" in Mr Cameron's Brussels agreement to change the DUP's Eurosceptic position.
On a momentous weekend in UK politics:
Mr Cameron has said the referendum represents "one of the biggest decisions this country will face in our lifetimes", but he faced open defiance from his own front bench team.
Ms Villiers said there were "risks on both sides of this debate" but the "safer option" was to leave.
In a further blow, Mr Johnson last night confirmed he would be campaigning to leave the EU.
"I don't think that anybody can claim that this is fundamental reform of the EU or of Britain's relationship with the EU," he said.
His announcement is a huge boost for the Out campaign, potentially giving it a popular figurehead able to connect with voters in a way few other politicians can manage.
Amid chaotic scenes, Mr Johnson insisted that he had agonised over the decision before finally declaring his hand.
"The last thing I wanted was to go against David Cameron or the Government, but after a great deal of heartache I don't think there is anything else I can do," he said.
"I will be advocating vote leave... because I want a better deal for the people of this country to save them money and to take back control."
Earlier, Mr Cameron had issued a last-ditch appeal for the London Mayor not to align himself with "outers" like Ukip leader Nigel Farage and Respect's George Galloway.
"I think the prospect of linking arms with Nigel Farage and George Galloway and taking a leap into the dark is the wrong step for our country," he said.
Mr Johnson's declaration drew a scathing response from Conservative former deputy Prime Minister Lord Heseltine, who branded it "illogical".
Within hours of Mr Cameron calling the referendum on Saturday, Northern Ireland's leaders set out their positions.
Mrs Foster said: "The DUP has always been Eurosceptic in its outlook. "At every stage in this European negotiation process we had hoped to see a fundamental change to our relationship with Europe," she said.
"In our view we see nothing in this deal that changes our outlook. Therefore we will on balance recommend a vote to leave the EU."
Mr McGuinness said: "It is clear that a majority of people in the North place great value on our membership of the European Union and want it to continue."
The SDLP and the Alliance Party are to campaign for the UK to remain in the EU.
The Ulster Unionist Party is still considering its position.
While David Cameron was widely mocked in the British Press for securing what many saw as cosmetic reforms at last week's Brussels summit, newspapers in Europe saw it as profoundly meaningful and wondered if this could lead to further unpicking of the European Union.
Alliance: Party is "unashamedly a pro-European party", and while it will campaign to remain in, says it is not blind to the reforms needed. A vote to exit Europe would leave the UK weak and divided, it claims.