Holding another referendum on the EU would “break faith with the British people”, Theresa May will warn MPs.
Former PMs John Major and Tony Blair are among those urging a new referendum if MPs cannot agree on a way forward.
But the prime minister will argue that it would do “irreparable damage to the integrity of our politics” and would “likely leave us no further forward”.
Last week she called off a Commons vote on her Brexit deal, admitting it was likely to be heavily rejected.
The UK is due to leave the EU on 29 March 2019 – the deal sets out the terms of exit and includes a declaration on the outline of the future relations between the UK and the EU. But it only comes into force if the UK and European Parliaments approve it.
The prime minister has signalled MPs will now vote on this early next year, and no later than 21 January.
But Labour and other opposition parties, as well as some Tory Brexiteers say a decision is needed now, so alternative options can be considered if Mrs May’s deal is rejected.
They are seeking to force a vote before the Christmas recess begins on Thursday, although the BBC’s Norman Smith said it was not clear how they could do this.
Potential “Plan B” options include:
Calls for another referendum have grown in recent weeks amid signs a majority of MPs are opposed both to the deal on the table but also leaving the EU without any kind of agreement.
Mr Blair said last week that after 30 months of negotiation, giving the final say to the people would become the “logical” outcome if there was a deadlock and every other option had been exhausted.