Changes in climate are expected to influence discharge of the lower Mississippi River, but projections disagree on whether discharge will increase or decrease over the coming century. Using a reconstructed median peak annual flow for the past 1,500 years based on geomorphic scaling laws, we show that discharge on the lower Mississippi River decreased during the Medieval era (c. 1000–1200 CE)—a period of regionally warm and dry conditions that serves as a partial analog for projected warming. These changes in discharge inferred from channel morphology track discharge simulated in the Community Earth System Model Last Millennium Ensemble. Simulations show that decreased Medieval era discharge is driven primarily by regionally enhanced evapotranspiration. Our findings are consistent with 21st century projections of decreased discharge on the lower Mississippi River under moderate greenhouse forcing scenarios, and demonstrate consistency between reconstructed and simulated discharge over the last millennium.