Quitting the European Union would leave households £4,300 a year worse off, George Osborne warned as he prepared to release in-depth Treasury analysis on the cost of Brexit.
Britain's economy would shrink by 6% by 2030 if the country replicated Canada's trading agreement as advocated by Boris Johnson, according to the Chancellor.
The 200 page Government report assessing the long term costs and benefits of EU membership and life outside shows the country would be left "permanently poorer".
In an article for The Times, Mr Osborne said: "The conclusion is clear: for Britain's economy and for families, leaving the EU would be the most extraordinary self-inflicted wound."
The study will say none of the alternative options to full EU membership would leave Britain with a quota-free, no-tariff access to a single market of half a billion consumers.
Mr Osborne added: "The Treasury analysis shows that under all plausible alternatives to British membership of the EU we would have a less open and interconnected economy -- not just with Europe but, crucially, with the rest of the world.
"There would be less trade, less investment and less business. Leave the EU, and the facts are: Britain would be permanently poorer. Britain's families would be permanently poorer too."
London's mayor said the June 23 referendum was on a "knife edge" and attacked the "usual suspects" that claim Britain must remain in to protect economic prosperity.
In his Daily Telegraph column, Mr Johnson wrote: "All the usual suspects are out there, trying to confuse the British public and to persuade them that they must accept the accelerating loss of democratic self-government as the price of economic prosperity.
"We have heard from the IMF (who got the Asian crisis completely wrong), as well as the banks and the CBI, all of whom were wrong about the euro.
"Davos man - the kind of people whose club class air tickets are paid by the taxpayer, all the lobbyists and corporate affairs directors of the big companies: they are all increasingly nervous that they have been rumbled, that people can see the emperor has no clothes and that Britain could have a glorious future outside the EU.
"They all know that there is one event in the next few weeks that could remind the British people of at least one salient point in this debate - that this country has lost control of its frontiers - and that is another migration crisis on the borders of the EU, and within the EU itself."
Former cabinet minister John Redwood dismissed the headline findings of the Government's analysis.
He said: "The Prime Minister was one of the senior advisers working in the Treasury while John Major's government tried to keep this country in the EU's disastrous Exchange Rate Mechanism.
"The ERM destroyed jobs and caused misery for families across the country.
'The remainers were wrong then, and they are wrong now - people should not trust their judgement on the EU."
It comes as Chris Grayling takes to the campaign trail with Nigel Farage to warn Britain faces a "tidal wave" of new laws from the European Union if it remains part of the bloc.
Brussels has a locker full of new plans but is holding back until after the June 23 referendum, the Commons leader will insist.
Mr Grayling will make the claims at a Grassroots Out (GO) rally in Stoke-on-Trent as he joins forces for the first time with the Ukip leader.
The Tory Cabinet minister will say: "Things may seem a bit quiet in Brussels at the moment. There don't seem to be many new laws being brought forward.
"But don't be deceived. It's not a sign that they have suddenly seen the light. They're holding it all back until we've voted, in the hope that we won't realise that there is another tidal wave of 'more Europe' heading our way.
"A vote to remain isn't a vote for things the way they are today. It's a vote to be part of a relentless march of Europeanisation, with us less and less able to decide what's good for Britain. The Commission's locker is full of new ideas and new plans. If we vote to remain, the door of that locker will be opened wide the day after.