Eleven thousand years ago, large lakes existed in central and eastern North America along the margin of the Laurentide Ice Sheet. The large-scale North American climate at this time has been simulated with atmospheric general circulation models, but these relatively coarse global models do not resolve potentially important features of the mesoscale circulation that arise from interactions among the atmosphere, ice sheet, and proglacial lakes. Here we present simulations of the climate of central and eastern North America 11,000 years ago with a high-resolution, regional climate model nested within a general circulation model. The simulated climate is in general agreement with that inferred from palaeoecological evidence. Our experiments indicate that through mesoscale atmospheric feedbacks, the annual delivery of moisture to the Laurentide Ice Sheet was diminished at times of a large, cold Lake Agassiz relative to periods of lower lake stands. The resulting changes in the mass balance of the ice sheet may have contributed to fluctuations of the ice margin, thus affecting the routing of fresh water to the North Atlantic Ocean. A retreating ice margin during periods of high lake level may have opened an outlet for discharge of Lake Agassiz into the North Atlantic. A subsequent advance of the ice margin due to greater moisture delivery associated with a low lake level could have dammed the outlet, thereby reducing discharge to the North Atlantic. These variations may have been decisive in causing the Younger Dryas cold event.