Deposition of trona, nahcolite, and other Na-carbonate evaporite minerals in lakes is commonly closely associated with active volcanism, suggesting that the excess alkalinity required for their formation may arise from fluid-rock interactions involving hydrothermal waters that contain magmatic CO2. Paradoxically, the world’s largest Na-carbonate occurrence, contained within the Eocene Green River Formation in Wyoming, USA, was not associated with nearby active magmatism. Magmatism was active ∼200 km southeast in the Colorado Mineral Belt, however, suggesting that a river draining this area could have supplied excess alkalinity to Eocene lakes. Sedimentologic studies in southwestern Wyoming, along the course of the hypothesized Aspen paleoriver, document fluvial and deltaic sandstone with generally northwest-directed paleocurrent indicators. Sandstone framework grain compositions and detrital zircon ages are consistent with derivation from the Colorado Mineral Belt and its host rocks. These results provide the first confirmation of a fluvial connection to downstream Eocene lakes, and indicate that lake deposits may offer a unique perspective on upstream magmatic and hydrothermal histories.