This study aimed at quantifying the impacts of climate and land use changes on flood damage on different flood occurrences. A Hydrologic Engineering Center’s Hydrologic Modeling System (HEC-HMS) model was calibrated for the period 2005–2011 and validated in the period 2012–2017, and was used to generate hydrographs using rainfall during the period 2020–2039 from CNRM-CM5, IPSL-CM5A-MR, and MPI-ESM-LR climate models under Representative Concentration Pathways (RCPs) 4.5 and 8.5. A Hydrologic Engineering Center’s River Analysis System (HEC-RAS) model for use in generating inundation maps from hydrographs produced by HEC-HMS was calibrated and validated for 2010 and 2011 period, respectively. The climate and land use changes showed insignificant impacts on the extent of floods during 25-, 50-, and 100-year flood events, i.e., inundation in 2039 under RCP 4.5 is smaller than baseline (2000–2017) by 4.97–8.59 km2, whereas a larger difference of inundation is found for RCP 8.5 (0.39–5.30 km2). In contrast, the flood damage under RCP 4.5 (14.84–18.02 million US$) is higher than the baseline by 4.32–5.33 million US$, while the highest was found for RCP 8.5 (16.24–18.67 million US$). The agriculture was the most vulnerable, with a damage of 4.50–5.44 million US$ in RCP 4.5 and 4.94–5.72 million US$ in RCP 8.5, whereas baseline damages were 4.49–6.09 million US$. Finally, the findings are useful in the delivery of flood mitigation strategies to minimize flood risks in the lower Nam Phong River Basin.