Sir John Major and Tony Blair have warned that a vote to leave the EU would be a "historic mistake" which could break up the UK.
The former adversaries shared a platform at the Ulster University's Magee campus in Londonderry, and warned that Brexit could threaten Northern Ireland's hard-fought peace process.
Sir John said: "I believe it would be an historic mistake to do anything that has any risk of destabilising the complicated and multi-layered constitutional settlement that underpins stability in Northern Ireland."
Both men played crucial roles in the Northern Ireland peace process, and Sir John warned that the "wrong outcome on June 23 could "tear apart the UK".
Mr Blair hit out at the Leave campaign, claiming it puts an "ideological fixation" with Brexit ahead of the damage it would cause.
He said: "I say, don't take a punt on these people. Don't let them take risks with Northern Ireland's future. Don't let them undermine our United Kingdom.
"We understand that, although today Northern Ireland is more stable and more prosperous than ever, that stability is poised on carefully-constructed foundations.
But the pro-Brexit DUP deputy leader Nigel Dodds condemned the former prime minister's comments as "irresponsible nonsense".
He said: "Surely this is the most irresponsible talk that can be perpetuated in terms of Northern Ireland - very dangerous, destabilising and it should not be happening," he added during the business statement in the Commons.
Elsewhere, former US president Bill Clinton, whose 1995 visit to Northern Ireland was seen as a crucial moment in the peace process, said he was worried about the potential impact of Brexit on the province.
Writing in the New Statesman magazine, Mr Clinton said: "I was honoured to support the peace process in Northern Ireland. It has benefited from the UK's membership in the European Union, and I worry that the future prosperity and peace of Northern Ireland could be jeopardised if Britain withdraws."
The former president, who worked with Sir John and Mr Blair on the peace process, added: "Transatlantic co-operation is essential, and that co-operation is strongest when Europe is united ... I hope you will stay."
Both former prime ministers had integral roles in helping to end the sectarian violence which blighted Northern Ireland for decades.
In 1993, Sir John and Irish prime minister Albert Reynolds delivered the Downing Street Declaration which argued for self-determination on the basis of consent and paved the way for the IRA ceasefires the following year.
Sir John told the audience of teenage schoolchildren who had packed into Magee's Great Hall: "I carried this forward and Tony completed it."
Five years later, in 1998, the British and Irish governments concluded the historic Good Friday Agreement which cemented the stability and laid the foundations for the devolved power-sharing Stormont Executive.
Here are some of the claims made by the two camps:
Remain camp says:
Leave camp says:
