David Cameron and Boris Johnson are set to clash in the Commons as the Prime Minister lays out his case for staying in the European Union.
As the referendum battle gets under way for real, Mr Cameron is due to give MPs details of the new membership deal he struck with EU counterparts following marathon talks in Brussels.
The premier has insisted he managed to win "special status" for the UK, with restrictions on benefits for migrants and an exemption from "ever closer" union.
But Mr Cameron is likely to get a rough ride from Tory backbenchers and half-a-dozen Cabinet ministers who have already declared they will be voting for Brexit in the national poll on June 23.
Sources close to Mr Johnson - who has effectively put himself at the head of the Out campaign by announcing his support - confirmed that the London Mayor and MP is due to attend the statement and will seek to ask a question.
Defence Secretary Michael Fallon denied that Mr Johnson's dramatic move was a "big blow" for those who want to stay in the EU, saying the "overwhelming majority" of the Cabinet backed Mr Cameron.
"I think that was expected. I don't think anyone is particularly surprised by that," he told BBC Radio 4's Today programme. "People are going to take different views on this, it is a matter of judgment. The overwhelming majority of the Cabinet have decided to back the PM in the special deal he has got back from Brussels and Boris has taken the opposite view.
"Obviously you would have liked more support from Boris but he has taken his individual view."
He added: "We have made it clear that there are going to be disagreements. The PM, to his credit, is allowing members of the Cabinet to dissent, he is allowing Tory MPs to have a different view.
"But in the end, when it is all over and the votes have been counted, then you can be sure that the Government will come together again and continue the programme that we got elected on last year."
Mr Fallon rejected suggestions from Work and Pensions Secretary Iain Duncan Smith that the EU was actually undermining Britain's security because potential terrorists were free to move between countries.
"At the moment our security, our defence, rests on Nato, not on the EU," he said. "But the EU adds to that security. I don't know any member of Nato that wants us to leave the EU because the EU can do things that Nato cannot.
"For example we were able to persuade the rest of Europe to apply sanctions against Russia after the annexation of the Crimea and its interference in Ukraine ...
"It is through the EU you exchange criminal records and passenger information and work together as counter-terrorism."
He also dismissed the idea that Britain could return to a "golden age" where it had full sovereignty without suffering serious consequences.
"The difficulty is this. If you got back to this sort of golden age where our parliament was absolutely sovereign, you would still have the EU next door," Mr Fallon said. "You would still have the EU taking decisions that affect our trade and our businesses and our way of life and the argument is this - isn't it better to still be there, however frustrating it is, at the table shaping those regulations, leading Europe in the direction you want, protecting your national interests, or should you go out and pursue this illusion of separate sovereignty all on your own without these partnerships and alliances."
Mr Johnson's announcement ended months of speculation about his intentions.
Writing in his weekly column in The Daily Telegraph, the mayor said the referendum offered a "once in a lifetime chance" to deliver "real change" in Britain's relations with her European neighbours.
"There is only one way to get the change we need - and that is to vote to go; because all EU history shows that they only really listen to a population when it says 'no'," he said.
As it was, voters could already see the "impotence" of national elected politicians in dealing with issues such as immigration.
"That enrages them; not so much the numbers as the lack of control. That is what we mean by loss of sovereignty - the inability of people to kick out, at elections, the men and women who control their lives," he said.
"We are seeing an alienation of the people from the power they should hold, and I am sure this is contributing to the sense of disengagement, the apathy, the view that politicians are 'all the same' and can change nothing, and to the rise of extremist parties."
Leaving his London home by bicycle this morning, Mr Johnson said he was focused on his work at City Hall.
"There will be plenty of time to talk about Europe and the great future that Britain can have outside the EU in the next few weeks," he told reporters.
Vote Leave chairman Lord Lawson hailed Mr Johnson's decision.
"I am delighted that he has come out for leaving the EU ... He is a superb campaigner and he is a great asset to the cause," he told Today.
The peer insisted the UK would be able to establish a free trade agreement with the EU "pretty swiftly".
He said it was "totally irrelevant" that it had taken Canada seven years to reach a trade deal with the EU.
"Canada did what it did, we shall do what we shall do," Lord Lawson said.
"We would negotiate. We have an excellent civil service, we have a competent government. We will negotiate an agreement so that we are once again independent, once again we are a self-governing country."
Mr Johnson's father Stanley Johnson, a former MEP and chairman of the Environmentalists for Europe group, said the mayor had made a "well-thought-out move" but denied he was merely positioning for the impending Tory leadership contest.
"I think he has done a really well-thought-out move. When I say move, it is a move in the sense it represents his deep conviction that at this moment this is what he needed to do," he told Today.
"Honestly, I think to say this is a careerist sort of move would be a total travesty. I cannot think of any more career-ending move than to do what he did yesterday, in the sense that he is leaving the mayoralty in May. If he wanted to get a nice job in the Cabinet on May 8, this is not the way to do it.
"I personally accept it because I much prefer to be a small fish in a bigger pond than a big fish in a small pond. That is the issue and Boris has posed that very clearly today and we should all be grateful to him for that."
Asked whether in a year's time people would be saying this was the moment that the mayor put himself on course to become prime minister, Mr Johnson replied: "Who can say?"