<p>Lake Manzala, one of Egypt’s largest coastal lakes, has experienced substantial environmental change due to human pressures and fluctuations in the quantity and quality of drainage water inflows. In recent years, drainage water reuse in agriculture has become increasingly important for improving national water management and supporting food security, with potential consequences for the lake’s ecosystem. Nonetheless, the impacts of the Bahr El-Baqar Wastewater treatment plant and the Egyptian Lakes Development Project (ELDP) on lake extent and soil salinization remain insufficiently evaluated. This study assesses the effects of increasing drainage water reuse in agriculture on Lake Manzala’s surface water area and adjacent soil salinity from 2016 to 2022. An integrated Python-based Google Earth Engine framework was developed using Sentinel-2 imagery to compute the Normalized Difference Water Index (NDWI), Normalized Difference Vegetation Index (NDVI), and Normalized Difference Salinity Index (NDSI), and to analyze these indices alongside secondary hydrological data. This work supports Sustainable Development Goal 6 by advancing tools for water-resources monitoring and management. Results indicate that the lake’s surface area increased by 21% in summer and 16% in winter between 2016 and 2022. This expansion associated with a 27% increase in treated wastewater discharged into the drainage system, which likely contributed to increased inflows to the lake. Over the same period, drainage water salinity increased by 8%, suggesting possible long-term risks to lake ecology and adjacent agricultural lands. These findings underscore the need to balance drainage water reuse in agriculture with adequate freshwater inflows and provide an automated monitoring framework and baseline for evaluating hydrological variability and large-scale water-management interventions in the Eastern Nile Delta.</p>