During the Pleistocene glacial periods, glaciers dammed the Clark Fork River Valley creating Glacial Lake Missoula. The ice dams broke periodically and at that time the Clark Fork River carried more water than the combined flow of all of the streams of the world: The Missoula Floods, also known as the Spokane Floods or the Bretz Floods, would rush down the Clark Fork and the Columbia River, flooding much of eastern Washington and the Willamette Valley in western Oregon. After the rupture, the ice would reform, recreating Glacial Lake Missoula. During the last deglaciation it is estimated that a cycle of flooding and reformation of the lake lasted an average of 55 years and that the floods occurred several times over the 2,000-year period between 15,000 and 13,000 years ago. There is evidence of at least twenty-five massive floods, the largest discharging 13 times the Amazon River. Estimates for the peak flow rate of the largest flood include 17 cubic kilometers per hour and range up to 60 cubic kilometers per hour. The maximum flow speed approached 80 mph.

It has been estimated that the oldest of the Pleistocene Missoula floods happened before 1.5 million years ago. Because of the fragmentary nature of older glaciofluvial deposits, which have been largely removed by subsequent Missoula floods, the exact number of older Missoula floods cannot be estimated with any confidence.