A sustainability assessment of water resources is essential for maintaining regional sustainable development. In this study, a comprehensive assessment of changes in the sustainability of the water resource system in Beijing from 2008 to 2018 was conducted on the basis of the driver-pressure-state-impact-response (DPSIR) model. To reflect the impacts of humans on the water consumption and pollution of water resources, the water footprint was considered. In addition, key factors that affect the sustainability of water resources were filtered by the modified entropy method. The results indicated that all drivers, pressures, states, impacts, and responses demonstrated increasing tendencies. As a result, a remarkable improvement in the sustainability of the water system, which was mitigated from an alert state to a good state, was achieved due to the comprehensive effect of the indexes. From these results, we inferred that the sustainability of regional water resources could only be achieved through a comprehensive consideration of regional social, economic, and environmental water systems and climate change. Therefore, formulating medium- and long-term urban, economic, and water development plans and adjusting medium- and short-term water utilization programs could contribute to the sustainable utilization of regional water resources.