During the late Pleistocene, multiple floods from drainage of glacial Lake Missoula further eroded a vast anastomosing network of bedrock channels, coulees, and cataracts, forming the Channeled Scabland of eastern Washington State (United States). However, the timing and exact pathways of these Missoula floods remain poorly constrained, thereby limiting our understanding of the evolution of this spectacular landscape. Here we report cosmogenic 10Be ages that directly date flood and glacial features important to understanding the flood history, the evolution of the Channeled Scabland, and relationships to the Cordilleran Ice Sheet (CIS). One of the largest floods occurred at 18.2 ± 1.5 ka, flowing down the northwestern Columbia River valley prior to blockage of this route by advance of the Okanogan lobe of the CIS, which dammed glacial Lake Columbia and diverted later Missoula floods to more eastern routes through the Channeled Scabland. The Okanogan and Purcell Trench lobes of the CIS began to retreat from their maximum extent at ca. 15.5 ka, likely in response to onset of surface warming of the northeastern Pacific Ocean. Upper Grand Coulee fully opened as a flood route after 15.6 ± 1.3 ka, becoming the primary path for later Missoula floods until the last ones from glacial Lake Missoula at 14.7 ± 1.2 ka. The youngest dated flood(s) (14.0 ± 1.4 ka to 14.4 ± 1.3 ka) came down the northwestern Columbia River valley and were likely from glacial Lake Columbia, indicating that the lake persisted for a few centuries after the last Missoula flood.