John Major has accused Brexit campaign leaders of "fuelling prejudice on immigration" and "morphing into Ukip".
The former Prime Minister will say in a speech later they have "crossed a boundary" and now risked creating long-term divisions in the country.
And he warn a Brexit would trigger a bitter backlash from Leave voters when they realise they have been misled by falsehoods.
In a speech at Oxford University, Major - whose premiership was torn apart by divisions over Europe - will say: "As the Leave arguments implode one by one, some of the Brexit leaders morph into Ukip, and turn to their default position - immigration. This is their trump card.
"I urge them to take care, this is dangerous territory that - if handled carelessly - can open up long-term divisions in our society."
The Tory grandee added Britain could also lose vital immigrants if it quits the EU.
He will add: "If we were to leave Europe, we could exclude more EU citizens - such as the 54,000 EU migrants now working as doctors, or nurses or ancilliaries in our health service, or the nearly 80,000 working in social care.
"We could exclude skilled workers like builders and plumbers - or unskilled labour that takes jobs that are unappealing to the British.
"In short, the people we could most easily keep out are the very people we most need."