Late Miocene and early Pliocene sediments exposed along the lower Colorado River near Laughlin, Nevada, contain evidence that establishment of this reach of the river after 5.6 Ma involved flooding from lake spillover through a bedrock divide between Cottonwood Valley to the north and Mohave Valley to the south. Lacustrine marls interfingered with and conformably overlying a sequence of post–5.6 Ma fine-grained valley-fill deposits record an early phase of intermittent lacustrine inundation restricted to Cottonwood Valley. Limestone, mud, sand, and minor gravel of the Bouse Formation were subsequently deposited above an unconformity. At the north end of Mohave Valley, a coarse-grained, lithologically distinct fluvial conglomerate separates subaerial, locally derived fan deposits from subaqueous deposits of the Bouse Formation. We interpret this key unit as evidence for overtopping and catastrophic breaching of the paleodivide immediately before deep lacustrine inundation of both valleys. Exposures in both valleys reveal a substantial erosional unconformity that records drainage of the lake and predates the arrival of sediment of the through-going Colorado River. Subsequent river aggradation culminated in the Pliocene between 4.1 and 3.3 Ma. The stratigraphic associations and timing of this drainage transition are consistent with geochemical evidence linking lacustrine conditions to the early Colorado River, the timings of drainage integration and canyon incision on the Colorado Plateau, the arrival of Colorado River sand at its terminus in the Salton Trough, and a downstream-directed mode of river integration common in areas of crustal extension.