The formation of the Kelso Dunes in the eastern Mojave Desert, California, was a landscape-changing event triggered by an increase in sediment supply that followed the incision of Afton Canyon by the Mojave River ca. 25 ka. Eastward migration of sand dunes occurred along a well-defined eolian transport corridor. Dunes temporarily blocked washes resulting in substantial aggradation of eolian and fluvial sediments. Stratigraphic exposures reveal numerous fining-up sequences with interbedded eolian sands that provide evidence of dune dams and subsequent aggradation. Luminescence ages reveal that dune blocking and aggradation correspond to a regional pulse of alluvial fan sedimentation that occurred ca. 14–9 ka. Meanwhile, relative landscape stability occurred downstream of dune dams, resulting in the formation of a moderately developed soil on abandoned fluvial deposits. The next pulse of alluvial fan activity ca. 6–3 ka likely resulted in the breaching of the dune dams, followed by incision. Eolian system sediment state theory suggests that eolian activity in the Mojave Desert is closely tied to enhanced sediment supply, primarily related to the Mojave River–Lake Mojave system. Our data suggests that Intermittent Lake Mojave I, ca. 26–22 ka, triggered a large dune-building event that impounded massive amounts of sediment derived from alluvial fans deposited during the Pleistocene-Holocene transition. Breaching of dune dams and sediment recycling may have also increased sediment supply that contributed to late Holocene eolian activity. This profound impact on the regional geomorphology highlights the critical importance of eolian-fluvial interactions in desert environments.