Freshwater is essential not only for human health but also for the ecosystems that sustain our food supply. However, pollution, overexploitation, and climate change increasingly threaten the sustainability of this vital resource. This study investigates the ongoing degradation of freshwater resources resulting from anthropogenic pressures and climatic variability. It focuses on two strategic watersheds in Algeria, the Cheliff and the Seybouse, adopting a systemic and transdisciplinary approach grounded in the “One Health” conceptual framework. The objective aims to understand the interactions between human activities, ecosystems, and public health by analyzing pollution sources, hydrological dynamics, and institutional responses. The study highlights the presence of emerging pollutants, primarily from agricultural, industrial, and urban discharges, and advocates for integrated contaminant management. It proposes sustainable solutions such as phytoremediation, improved agricultural practices, and involvement of local communities. Finally, the research emphasizes the urgent need to strengthen water governance through enhanced monitoring, prevention, and adaptive strategies to ensure water security, ecosystem health, and sustainable development.