"It did not take the Brexit vote to understand that low growth, rising inequality, and a lack of jobs have combined with social and geopolitical concerns to fuel the rise of populism and inward-looking forces," Lagarde said in a speech in Washington, according to her prepared remarks.
"The greatest challenge we face today is the risk of the world turning its back on global cooperation -- the cooperation which has served us all well," the IMF managing director said at an event hosted by the Center for Global Development.
"If we are not able to provide this coming generation with a livelihood and a chance to share in global welfare, we should be prepared for migration and political strife at an unprecedented level," she warned.
"And let us have no illusions that this would stop at the water's edge, or at borders secured by a wall or chain-link fence."
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Europe is battling its worst migration crisis since World War II as more than a million migrants, including many refugees escaping conflict in Syria and other states, have flooded in.
In the United States, the presumptive Republican presidential nominee Donald Trump has vowed that, if elected, he would make Mexico build a wall along its US border to keep out illegal immigrants.