Water quality issues in Ethiopia necessitate the implementation of the Water Safety Plan (WSP) to safeguard drinking water. Despite its benefits, WSP implementation is underutilized, a situation exacerbated by urbanization, agriculture, pollution, and climate change. This study evaluated water supply system vulnerability and delineated protection zones in the Upper Awash River subbasin. By employing the DRASTIC model, the National WASH Inventory-2 (NWI-2), and qualitative methods, this research aims to integrate the NWI-2 with vulnerability assessments. The study revealed that, among 2864 schemes, only 14.4% had a water safety plan, while 20.7% practiced water safety, and 6% reported the occurrence of waterborne diseases. Over 39.23% of the schemes were in high vulnerability areas, 12.32% were in very high vulnerability areas, and only 8% were in low vulnerability areas. The validation revealed a 61.7% association between the vulnerability indices and nitrate concentration. The strengths of the strategy included coordination and guideline development, but challenges such as institutionalization, catchment protection, the legal framework, and climate information remain for the Water Safety Plan. To promote public health, these findings help to demonstrate and integrate the NWI-2 with vulnerability assessments to protect drinking water sources. The conclusion also calls for all concerned authorities to implement water source protection, emphasizing the use of GIS technology and the adoption of integrated watershed management practices, which encompass regulatory control and conservation strategies. Furthermore, more research on the pollutant time of travel, assimilation capacity, and land use priorities is needed to delineate specific protection zones.