Britain leaving the EU could contribute to the "destruction" of the international order, David Miliband will warn.
The former foreign secretary, who quit frontline politics to head the International Rescue Committee (IRC) aid organisation, will enter the referendum debate with a warning against "unilateral political disarmament".
In a rare foray back into UK politics, he will give a speech urging "remain" campaigners not to "cede passion or patriotism to the other side" and arguing Brexit would be disastrous not just for the UK but the rest of the world.
Speaking in a personal capacity, he is expected to say: "Think about it. Unilateral political disarmament.
"No nation in human peacetime history, never mind Britain, has voluntarily given up as much political power as we are being invited to throw away on June 23. All thrown away in a vote to leave.
"For what? For a cold, hard lesson in the demon of hubris, born of delusion that the world owes us a break. A tragic miscalculation which weakens ourselves, our friends and the international order on which we depend.
He will go on: "Quitting Europe means giving up on our alliances, forsaking our position at the negotiating table, abandoning our international responsibilities and risks setting off a domino effect that strengthens our enemies and undermines our allies.
"The question of Britain's place in Europe, is not only one of what we 'get' out of Europe. It is also a question of whether we want to shore up the international order, or contribute to its dilution and perhaps even destruction.
"My point is that this is not just bad for Britain. It is very bad for the international order, and the aspirations for that order, on which we depend.
"There has been some discussion of how leaving Europe would create a splintering effect in the UK, sponsoring Scottish separatism just when the collapse of the oil price has sundered the argument for it. But it also threatens a domino effect around the world, at just the time we need stronger international co-ordination, not less.
"Think of the big questions that need to be tackled: whether global capitalism has more bust than boom; whether western values can be sustained in the face of global pressures; whether the climate crisis is past resolution; whether public services can survive the flight of capital from western tax authorities.
"All of them need more effective international co-ordination that is regional as well as global.
"It is said that the world is increasingly divided between firefighters and arsonists. For centuries, Britain has been a firefighter. We have always sought to balance great powers and check the abuse of power. There is no shortage of fires that need to be put out around the world at the moment.
"This is no time for Britain to join the ranks of arsonists, and there should be no doubt that Brexit would be an act of arson on the international order."
He will dismiss characterisations of the pro-EU campaign as "Project Fear" and said those pushing for Brexit were "Project Fantasy".
"Unilateral political disarmament is not a joke or a jape. It is a recipe for instability not order, derision not applause, a fall not pride.
"The character of our country, our place in the world, as well as our material wealth, are on the ballot paper, and those of us arguing for Britain to remain in the EU must not cede passion or patriotism to the other side."