Philip Hammond is to warn that "all the preparation in the world will not avoid the consequences" of a no-deal Brexit.
The Chancellor will say in a major speech on Tuesday that MPs calling for Britain to fall out of the EU without an agreement want to hijack the result of the referendum.
In one of his strongest attacks yet on a no-deal Brexit – an option the government is leaving open – Mr Hammond will declare that the scenario would knowingly… inflict damage on our economy and our living standards.
He will claim in his address to the CBI that there is no mandate for a no-deal exit and that ministers have an absolute obligation to protect Britain’s jobs, businesses and future prosperity.
Britain remains on the path to leave the EU without a deal on 31 October.
Mr Hammond’s intervention comes hours after his number two at the Treasury, Liz Truss, said the UK needed to prepare for a no-deal divorce if an agreement is not ratified in parliament by the next Brexit date.
If we don’t do that, this could be a massive problem for us in terms of trust, for us in terms of politics, but also our economy, the Treasury chief secretary told a Daily Telegraph event.
She added the UK was ready, blasted people promoting ridiculous scare stories about no-deal and asked: What are we so scared of?
Earlier, Tory leadership-hopeful Esther McVey also said it was essential the UK leave the EU by 31 October.
She warned there would be no more backsliding and confirmed that if it means without a deal, we’ll be out.
The issue is set to underpin the race to replace Theresa May in Number 10.
A group of around 60 Tory MPs have set up a One Nation Conservatism group that could see them try to block a no-deal candidate winning the contest.
One of its members, Sir Nicholas Soames, told Sky News: I don’t think we will want to vote for anyone who is going to propagate a no-deal situation.
Prime Minister Theresa May has tried three times to get a divorce deal through parliament that would have seen the UK leave the bloc on 29 March.
But Tory Brexiteers and the government’s confidence and supply partners have united with opposition and Remainer MPs to vote it down each time.
Mrs May will launch a final attempt to pass the bill that would pave the way to a deal becoming law in the first week of June.
Brexit Secretary Stephen Barclay has told Sky News’ Sophy Ridge on Sunday that no-deal Brexit preparations must be brought forward at pace if MPs reject the agreement again.
(c) Sky News 2019: No-deal Brexiteers want to ‘hijack’ referendum result, says chancellor