Boris Johnson has urged voters to seize a once-in-a-lifetime chance to change the course of European history and take Britain out of the EU.
With just three days to go to polling in the referendum and the result apparently too close to call, both sides are preparing for a final push for votes.
On Sunday night, David Cameron issued an impassioned appeal to voters not to give up on the EU but "stay and fight" Britain's corner in the way that had made the country great in the past.
Mr Johnson used his weekly column in the Daily Telegraph to say the country was facing a "moment of fundamental decision" with a chance to transform Britain's democratic arrangements for the better.
"Now is the time to believe in ourselves, and in what Britain can do, and to remember that we always do best when we believe in ourselves. This chance will not come again in our lifetimes, and I pray we do not miss it," he wrote.
"You can change the whole course of European history - and if you vote Leave, I believe that change will be overwhelmingly positive."
Appearing in front of a BBC Question Time audience in Milton Keynes, Mr Cameron said a vote for Brexit on Thursday would be "irreversible" as he urged people to "think very carefully" before casting their votes.
The Prime Minister was clearly stung by one man in the audience who likened him to a "21st century Neville Chamberlain waving a piece of paper in the air saying to the public, 'I have this promise'" - a reference to the appeasement of Hitler in the 1930s.
He rejected the comparison of the EU to a "dictatorship" and invoked the wartime spirit of Winston Churchill to urge voters to carry on the fight for British values within Europe.
"I don't think Britain at the end is a quitter. I think we stay and fight. That is what we should do. That is what made our country great and that's how it will be great in the future," he said.
"At my office I sit two yards away from the Cabinet Room where Winston Churchill decided in May 1940 to fight on against Hitler - the best and greatest decision anyone has made in our country.
"He didn't want to be alone, he wanted to be fighting with the French and with the Poles and with the others, but he didn't quit. He didn't quit on Europe, he didn't quit on European democracy, he didn't quit on European freedom.
"We want to fight for those things today. You can't win, you can't fight, if you are not in the room. You can't win a football match if you are not on the pitch."
Mr Cameron rounded on the Vote Leave campaign, headed by Mr Johnson and Michael Gove, over "untrue" claims about the prospects of Turkey joining the EU, the creation of a European army, and the scale of the UK's contribution to Brussels.
"It would be a tragedy if we damaged our economy, wrecked job prospects in our country, on the basis of three things that are completely untrue," he said.
During the at times heated 45-minute debate, the Prime Minister came under pressure over the Government's failure to bring down immigration numbers, with one woman warning public services would be "flooded" if Britain remained in the European Single Market.
An exasperated Mr Cameron admitted: "There is no silver bullet on this issue. There is no simple way of solving this issue."
Earlier, with immigration set to be one of the key issues in the remaining days of the campaign, Vote Leave seized on an admission by Labour leader Jeremy Corbyn that there could be no upper limit as long as Britain was in the EU.
Concerns about immigration have widely been blamed for driving traditional Labour voters to swing heavily towards Leave.