The prime minister is to warn that peace in Europe could be at risk if Britain votes to leave the EU.
The UK has regretted “turning its back” on Europe in the past, David Cameron will say as he invokes history to make his case for staying in the EU.
He will say the UK’s national story is intertwined with Europe’s.
Boris Johnson, who wants Britain to leave the European Union, will make a “cosmopolitan case for Brexit” in a speech later.
The former mayor of London will speak before starting a battle bus tour of the country on behalf of the Leave campaign later this week.
There is just over six weeks to go until the 23 June referendum which will decide whether the UK remains in or leaves the EU.
With last week’s elections now out of the way, the referendum campaign will intensify with speeches from the most high-profile figures on both sides of the campaign.
Mr Cameron will argue that the EU – with Britain in it – has helped bring together countries that had been “at each others’ throats for decades”.
He will warn that the peace and stability which Europe has enjoyed in recent years cannot be guaranteed, and will ask whether that “is a risk worth taking”.
The PM will argue that continued co-operation is in keeping with the country’s finest traditions and the sweep of its history.
‘Risk worth taking?’
While Europe has largely been at peace since 1945, Mr Cameron will say it is barely two decades since the Bosnian war cast a dark shadow over the continent while, more recently, Russia has been at war with Georgia and Ukraine.
“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.”
He will argue that the European Union despite its faults has helped reconcile countries that have been at war with each other and “isolationism has never served this country well”.
“The truth is this: what happens in our neighbourhood matters to Britain,” he will add.
“That was true in 1914, in 1940 and in 1989. Or, you could add 1588, 1704 and 1815… And if things go wrong in Europe, let’s not pretend we can be immune from the consequences.”
Key Leave figures like Mr Johnson, Michael Gove and Iain Duncan-Smith say the UK needs to be more self-confident and outward-looking, warning that future integration within the eurozone further threatens the UK’s autonomy and sovereignty.
They reject claims that the UK’s global standing will be undermined by not being in the EU, pointing to its membership of the UN Security Council and Nato – which both pre-date its joining the European Economic Community – and its strong bilateral relationship with the US.
On Sunday, Mr Gove said the UK could pull out of the EU’s single market without damaging trade, and clashed with cabinet colleague George Osborne on the issue.
The justice secretary said the UK would not be “punished” for leaving the EU by having tariffs placed on its exports.
He said he could “not imagine” Germany putting up trade barriers which would threaten their own exports into the UK.