Sir Vince Cable will urge “sensible grown-ups” in other parties to join forces with the Liberal Democrats to prevent Brexit becoming a “disaster”.
In his first leader’s speech, he will urge “political adults” in Labour and the Conservatives to put aside tribal loyalties to ensure the UK remains in the single market and customs union.
He will defend his call for a further referendum on the outcome of EU talks.
“We believe the public have a right to change their mind,” he will say.
The 74-year old became leader this summer after Tim Farron’s resignation in the wake of June’s snap general election – in which the party failed to make the gains it had hoped for.
The veteran politician and former business secretary has said his party members face the “fight of their political lifetimes” if they are to persuade the British public to reverse their decision last year to leave the EU.
While he has warned that the Lib Dems must not become a single-issue party or as he put it – “UKIP in reverse” – he will place his party’s goal of stopping Brexit front and centre of his keynote speech to activists in Bournemouth.
He will accuse the government of mismanaging the negotiations and warn that “disaster looms” if it does not change tack and prioritise trade and jobs in the final Brexit settlement.
Recognising that the Lib Dems alone cannot change the direction of government policy, he will urge Labour leader Jeremy Corbyn to “get off the fence” when it comes to putting the economy first in the talks.
“What the people want, what the country now desperately needs is some political adults,” he will say.
“That’s you, that’s us. Fortunately we are not alone. There are sensible grown-ups in the Conservative Party and Labour Party and the Greens. And beyond them are millions of people deeply worried about what is happening.
“We have to put aside tribal differences and work alongside like-minded people to keep the single market and customs union, essential for trade and jobs.”
The Lib Dems did not make the progress they anticipated in June’s election, in which their pledge to give the public the final say on the terms of the UK’s withdrawal was the centrepiece of their offer to voters.
But Sir Vince will say the Lib Dems, unlike other parties, is “totally united” on Brexit and he will reaffirm his commitment to another referendum, refuting criticism that having another vote would be undemocratic.
“Let me be clear. This is not a call for a re-run – a second referendum – on Brexit. It is a call for a first referendum on the facts: when we know what Brexit means.
“We know that our call will, of course, be resented by Brexit fundamentalists and we will be denounced as traitors and saboteurs… But if their definition of sabotage is fighting to protect British jobs, public services, the environment and civil liberties, then I am a proud saboteur.”
Both the Conservatives and Labour have rejected the idea of a second referendum, saying people have already spoken when they voted to leave by 52% to 48% and the focus should be on getting the best deal.
But Sir Vince will suggest the row between Boris Johnson and the head of the UK’s statistics authority over the foreign secretary’s claim that Brexit could deliver a financial windfall of up to £350m a week for the NHS illustrates that leading Brexit supporters are “afraid of the facts”.
Arguing it would be legitimate to re-open the question of Britain’s future in Europe if circumstances change, he will suggest leading Brexit supporters “now believe in the slogan of dictators everywhere: one person, one vote, once”.
Ahead of Tuesday’s speech, which will close the four-day conference, Sir Vince said he was optimistic about the party’s future as a moderate force in the centre ground of British politics.