David Cameron will warn that Europe's peace could be jeopardised if Britain votes to leave the EU, as he suggests the referendum contest will form a pivotal moment in the continent's history.
The Prime Minister will issue the rallying cry as the EU contest enters a new phase, with both sides stepping up their activities in the run-up to the June 23 vote.
Mr Cameron will stress the long, historic links with continental Europe - and highlight the sacrifice of British military personnel to ensure the peace of the continent as he makes a "patriotic case" for a Remain vote.
But he will also warn that the peace which Europe has enjoyed in recent years cannot be guaranteed "beyond any shadow of doubt" and ask "is that a risk worth taking".
He will rank 2016 alongside other turning points in European history including the year of the Spanish Armada in 1588, Blenheim in 1704, Waterloo in 1815, the First World War in 1914, the Battle of Britain in 1940 and the fall of the Berlin Wall in 1989.
"The European Union has helped reconcile countries which were at each others' throats for decades," he will say.
"Britain has a fundamental national interest in maintaining common purpose in Europe to avoid future conflict between European countries.
"And that requires British leadership, and for Britain to remain a member.
"The truth is this: what happens in our neighbourhood matters to Britain.
"That was true in 1914, in 1940 and in 1989. Or, you could add 1588, 1704 and 1815.
"It is just as true in 2016.
"Either we influence Europe, or it influences us.
"And if things go wrong in Europe, let's not pretend we can be immune from the consequences."
Within hours of Mr Cameron's address, Brexit campaigner Boris Johnson - now free from the constraints of office in London - will deliver his own speech before heading out on a campaign battle bus tour across the country later this week.
Setting out the long ties binding the UK to its neighbours Mr Cameron will say: "For good or ill, we have written Europe's history just as Europe has helped to write ours."
Mr Cameron will add: "The moments of which we are rightly most proud in our national story include pivotal moments in European history. Blenheim. Trafalgar. Waterloo.
"Our country's heroism in the Great War.
"And most of all our lone stand in 1940, when Britain stood as a bulwark against a new dark age of tyranny and oppression."
Both sides of the referendum debate have sought to use Winston Churchill to make their case, and Mr Cameron will say: "It wasn't through choice that we were alone. Churchill never wanted that. Indeed he spent the months before the Battle of Britain began trying to keep our French allies in the war, and then after France fell, he spent the next 18 months persuading the United States to come to our aid.
"And in the post-war period he argued passionately for Western Europe to come together, to promote free trade, and to build institutions which would endure so that our continent would never again see such bloodshed."
The Britain Stronger In Europe campaign released a video message from Second World War veterans to underline the Prime Minister's message.
Mr Cameron will say: "Whenever we turn our back on Europe, sooner or later we come to regret it.
"We have always had to go back in, and always at much higher cost.
"The serried rows of white headstones in lovingly-tended Commonwealth war cemeteries stand as silent testament to the price this country has paid to help restore peace and order in Europe."
Highlighting the bloodshed in the Balkans and Russian aggression in Georgia and Ukraine, he will say: "Can we be so sure that peace and stability on our continent are assured beyond any shadow of doubt?
"Is that a risk worth taking?"
"I would never be so rash as to make that assumption."
A Vote Leave spokesman said: "Claims that leaving the EU and taking back control would somehow lead to war smack of desperation from a campaign failing to make the case for the EU and our continued payment of £350 million to Brussels every week.
"The PM's words are deeply ironic given the EU's own border agency says the EU's borderless policy is making the whole of Europe less safe. The safe option is to vote Leave."