In a rallying cry to pro-EU MPs and peers, the former Prime Minister will accuse Theresa May of pursuing Brexit "at any cost" and warn it could lead to Scottish independence.
Mr Blair, who wants a second referendum and has pledged to campaign to keep the UK in the EU, will deliver his latest attack on Brexit in a powerful speech to Remain supporters.
His speech will also be seen as a signal that he would like to create a new pro-Remain political party made up of Blairites, Liberal Democrats and even some pro-EU Conservatives.
But Mr Blair will face a bitter backlash from leading Brexit supporters and puts himself at odds with Jeremy Corbyn, who last week ordered Labour MPs to vote for the Government's Article 50 bill.
Speaking only days before the bill is debated in the House of Lords, Mr Blair will say: "This is not the time for retreat, indifference or despair; but the time to rise up in defence of what we believe."
The Brexit Secretary David Davis admitted this week that the Government is expecting amendments to be passed by peers and predicted "ping pong" between the Commons and the Lords.
Mr Blair is making his speech to the Open Britain group, whose leading figures include LibDems Nick Clegg and Norman Lamb, Labour's Chuka Umunna and Pat McFadden and Tories Anna Soubry and Dominic Grieve.
Acknowledging that the will of the people should prevail, he will say: "But the people voted without knowledge of the true terms of Brexit. As these terms become clear, it is their right to change their mind.
"Our challenge is to expose relentlessly the actual cost, to show how this decision was based on imperfect knowledge which will now become informed knowledge; to calculate in easy to understand ways how proceeding will cause real damage to the country and its citizens, and to build support for finding a way out from the present rush over the cliff's edge.
"I don't know if we can succeed, but I do know we will suffer a rancorous verdict from future generations if we do not try."
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