Sediment eroded from continents during ice ages can be rapidly (<104 years) transferred via rivers to the deep-sea and preserved in submarine fans, becoming a viable record of landscape evolution. We applied chemical weathering proxies and zircon geo-thermo-chronometry to late Pleistocene sediment recovered from the deep-sea Mississippi fan, revealing interactions between the Laurentide ice sheet (LIS) and broader Mississippi-Missouri catchment between ca. 70,000 and 10,000 years ago (70 to 10 ka). Sediment contribution from the Missouri catchment to the Mississippi fan was low between 70 and 30 ka but roughly doubled after the Last Glacial Maximum (LGM). Therefore, pre-LGM glacial advance profoundly altered the vast Missouri drainage through ice dams and/or re-routing of the river, thereby controlling the transfer of continental debris and freshwater toward southern outlets.