Public services such as health and education could face £36 billion of cuts if the country votes to leave the European Union, George Osborne has warned.
The Chancellor warned the price of Brexit would be paid by British families, who would be £4,300 a year worse off according to Treasury analysis.
As well as that long-term impact, he warned that in the short term the country would face a "profound economic shock and real instability".
Britain's economy would shrink by 6% by 2030 if the country replicated Canada's trading agreement with the EU, as advocated by Boris Johnson, according to the Chancellor.
Mr Osborne said: "Under any alternative, we'd trade less, do less business and receive less investment.
"And the price would be paid by British families. Wages would be lower and prices would be higher.
"The most likely result is that Britain would be poorer by £4,300 per household. That is £4,300 worse off every year, a bill paid year after year by the working people of Britain."
He said the analysis produced by the Treasury was "serious and sober" and showed "British families will pay a heavy economic price if we leave the EU."
Mr Osborne rejected the claims of Leave campaigners that the country would benefit from the savings made by not contributing to Brussels' coffers.
Speaking in Bristol he said: "Don't believe the flimsy claim that at least we would get some money back by not paying our 1p on every £1 we raise in taxes to the European budget.
"We'd lose tens of billions of pounds in money for our public services, because our economy would be smaller and our families poorer.
"The most likely bill our public services would pay for leaving the EU is £36 billion.
"That's the equivalent of 8p on the basic rate of income tax."
Flanked by Cabinet ministers Liz Truss, Stephen Crabb and Amber Rudd, Mr Osborne said the June 23 referendum represented "the biggest decision for a generation - one that will have profound consequences for our economy, living standards and Britain's role in the world".
Voters should ask themselves "Are you better off or worse off if Britain leaves the EU? Does your family get more money or less? And is there more money or less available to your Government to pay for public services and tax cuts?"
Mr Osborne said it was "a complete fantasy" to suggest that the UK would be able to negotiate access to the single market without agreeing to accept the costs and obligations of EU membership.
"How could other European countries give us a better deal than they have given themselves?" he asked.
This meant the UK would have three options for its future relations with the EU - either for the status currently enjoyed by Norway, which makes payments to the EU and accepts free movement in return for access to the single market, or a bilateral free trade deal of the kind obtained by Canada, or gaining more limited access under the rules of the World Trade Organisation.
Meanwhile, the Chancellor claimed that the reforms negotiated by Prime Minister David Cameron offered a "huge prize" for the UK, which could increase its GDP by 4% over the coming years and would be worth thousands of pounds to the average household.