In the Chao Phraya River Basin, Thailand, water-related hazards, particularly river floods, flash floods and droughts, are increasingly causing damages to the local society, economy and environment due to changing climate and urbanization. As its impact, identification of key factors influencing the occurrence and severity of multiple water-related hazards at different temporal and spatial scales is therefore essential to further development of solutions for hazard reduction. The study identified through the analytic hierarchy process several key influence factors to water-related hazards, including precipitation, discharges, natural and green surface areas, and water storage, in the Upper Chao Phraya River basin, Thailand. These factors were then used for the assessments of individual and multiple hazards, as well as potential interventions for hazard reduction. A combination of several research methods was adopted for the hazard assessments, including simulation modelling, multi-criteria decision analysis, and spatial analysis based on both primary and secondary data sources. Eventually, spatial distribution of hazard levels at regional and local scales was mapped out to inform water-related multiple hazards and the potential of selected nature-based solutions to such hazards based on the data of specific years. It was found that increasing vegetation areas and having nature-based reservoirs can effectively improve water management in both wet and dry seasons, contributing to hazard reduction. It is expected that the assessments performed in this study can contribute to awareness-raising of water-related hazards and eventually enhance the preparedness of risk management in the studied areas.