Gordon Brown has warned the future of the union between England, Scotland, Wales and Northern Ireland is "more at risk" than at any time in 300 years.
The ex-prime minister said the United Kingdom risked "unravelling" due to Brexit and the "narrow nationalism" of the Conservative and SNP governments.
In a speech in London, he urged the "patriotic majority" to speak up against their values being "hijacked".
Brexit supporters have dismissed claims it could hasten Scottish independence.
Scotland voted overwhelmingly to stay in the EU in the 2016 referendum, as did Northern Ireland, while Wales and England voted to leave.
Boris Johnson, the favourite to succeed Theresa May as Conservative leader and prime minister, has pledged to bring different parts of the UK together if he wins power and address the economic and political disparities which fuelled the Brexit vote.
In a BBC interview, he said he recognised that parts of the UK felt "left behind".
However, he insisted that he would be prepared to take the UK out of the EU without a legally-binding agreement on the 31 October deadline.
Speaking to the Fabian Society, Mr Brown said such rhetoric was a "recruiting sergeant" for the SNP - whose leader Nicola Sturgeon has signalled there will be another independence vote in 2021 if the UK leaves the EU against Scotland's will.
A no-deal exit, he argued, was an "act of economic self-harm" which Mr Johnson and Brexit Party leader Nigel Farage were determined to make a "test of true patriotism".
Leaving without any mutually agreed basis for future co-operation would not only cause irreparable economic damage, Mr Brown said, but threaten the peace settlement in Northern Ireland and undermine the whole integrity of the union.
"Talking up no deal means renouncing the chance of a positive post-Brexit relationship with the continent and our major economic partners," he said.
"It is yet another example of an inward-looking, isolationist and dogmatic approach that has no economic logic and runs counter to our long-term national interest.
"And yet those who do not go down that road are accused of not being true patriots and of betraying Britain. Our patriotism has been hijacked by a narrow dogmatic nationalism."
Mr Brown played a key role in the No campaign in the 2014 Scottish independence referendum.
Criticising Mr Johnson's record on and respect for Scottish devolution, he said the former mayor of London would be under pressure to "play the English card" at the next election to try and win a Conservative majority "even at the cost of harming the union".
'No backdoor deal'
Amid , he warned of a repeat of the 2015 election, when David Cameron repeatedly argued a minority Labour government could offer an independence referendum as its price for SNP support.
"It is right to warn of the SNP's obsession with independence," he said.
"It is right too for us to remind Labour that as a party of the union it can never and must never made a backdoor deal with the SNP."
As a first step in rebuilding "trust" with Leave voters, he called for a series of citizens' assemblies across the UK, modelled on those in the Republic of Ireland, to examine "very real problems" such as concerns over immigration, low pay and lack of new manufacturing jobs.
He also called for tougher laws to eradicate Islamophobia and anti-Semitism and more emphasis on teaching about community relations in schools.
With the very survival of the United Kingdom under threat, he called for "new defenders" of the union to make themselves heard and tackle the "threat from these new nationalisms".
"I believe the union is today more at risk than at any time in 300 years," he added.
The SNP's former deputy leader Stewart Hosie said a no-deal Brexit would be "clearly contrary" to Scotland's wishes.
He told Sky News that if Mr Johnson or another future PM "ignored" Scotland over Brexit, "it leads us closer to independence".