With likely increases in probable maximum precipitation (PMP) in a changing environment, critical infrastructures such as major reservoirs and nuclear power plants are subject to elevated risk. To understand how factors such as PMP variability, climate change, land use land cover (LULC) change, antecedent soil moisture conditions, and reservoir storage may individually or jointly affect the magnitude of probable maximum flood (PMF), we conducted integrated hydro-meteorological simulation involving both the Weather Research Forecasting model and the distributed hydrologic model (DHSVM) over the Alabama-Coosa-Tallapoosa (ACT) River Basin. A total of 120 relative humidity–maximized PMP storms under historic and projected future climate conditions were used to drive DHSVM in current and projected future LULC conditions. Overall, PMP and PMF are projected to increase significantly over the ACT River Basin. Sources of meteorological forcing data sets and climate change were found to be the most sensitive factors affecting PMF, followed by antecedent soil moisture, reservoir storage, and then LULC change. The ensemble of PMP and PMF simulations, along with their sensitivity, allows us to better quantify the potential risks associated with hydro-climatic extreme events to critical infrastructures for energy-water security.