The de facto Deputy Prime Minister warned that a growing "indifference to the union" among English voters stands alongside the independence movement in Scotland as a threat to the existence of the UK as he addressed an audience in Edinburgh.
Mr Lidington said defending the union will be among the key qualities required in the next Prime Minister and backed Jeremy Hunt as the best candidate to keep the UK together.
"I do think the Union is under more threat than I've known previously in my lifetime," Lidington said.
"I'm a very strong Unionist but I think we need to be alive to the fact that there is a combination of nationalist feeling on the one hand and indifference or ignorance of the value of the union on the other that puts that achievement at risk."
Mr Lidington was addressing a conference at the Law Society of Scotland in Edinburgh to mark two decades of devolution and warned that the splintering of the United Kingdom would be "harmful to the interests" of all four of its constituent nations.
He added: "Each of us would be diminished - economically and in terms of global influence and global opportunity.
"And therefore it strikes me it is the duty of the next Prime Minister to do all in his power to uphold and strengthen the integrity of the United Kingdom and to win public support for that."
Lidington added that he was "shocked" by a weekend poll of Tory voters at the weekend which found a majority would accept Scotland leaving the UK as the price of securing Brexit.
He added: "The challenge is not just from a strong constituency of support for separatism in Scotland or for pressure from a change in demographic in Northern Ireland, it is in part from an English mood that is sometimes indifferent to the union and unaware that is the union and the efforts of the United Kingdom as a whole that can achieve far more than England would on its own."
A rise in English nationalism has been happening over the past 20 years, Mr Lidington acknowledged, with English supporters at rugby and football matches more likely to wave St Georges flags instead of Union Jacks which were more common a generation ago. Politicians faced a challenge, he admitted, to ensure this does not cross the line to become "adversarial" to others.
"There's a political and culture challenge to try to embrace English patriotism without that becoming English nationalism," he said.
"It is therefore in part about politicians finding language that is positive, that can taken pride in your achievements in your history as a country while not seeing that as something you have to judge in terms of being hostile or adversarial or envious or resentful of others."