AbstractAn increase in heavy precipitation associated with climate change has exacerbated flooding in the Eastern U.S. To assess regional flood risk with changing climatic conditions, we demonstrate the application of a novel hydrologic modeling framework that integrates climate projections with a coupled Noah‐MP land surface model and a two‐dimensional HEC‐RAS hydrodynamic model. We employ this framework along a 41 km reach of the Susquehanna River near Harrisburg, Pennsylvania, where recent flood damages exceeded $2 billion (2011 Irene and Lee floods). Historical and future 30‐year and 100‐year peak‐discharge estimates were compared to assess how flood risk might be altered due to climate change. Results indicate that precipitation increases from climate change do not always lead to increases in flood risk, because interplay of hydrological components in the watershed, which are considered by Noah‐MP, largely controls flooding severity. However, climate change is expected to increase the severity of extreme events; if a 50‐year flood (the recurrence interval of Tropical Storm Lee) occurred toward the end of the 21st century in the worst‐case emission scenario, then flood volume would increase by 40% and flood extent by 15%, due to an increase in soil moisture from a wetter overall climate.