Sulfides are usually associated with deposits of metals and coal. The reactive wastes from their exploitation, typically stored in piles and tailings dams, are often the mining sector’s primary source of environmental problems. The surrounding river waters can present signs of acid mine drainage, responsible for aquatic ecosystem degradation. So, the main target of the present study is to investigate the impact of this process on the water’s environmental quality and potential ecological risk. The study area is located at the Iberian Pyrite Belt, in an old sulfide exploitation, closed without environmental rehabilitation measures. The results exhibit high sulfate concentrations (410,601 mg/L) and potentially toxic elements, with prominence of Fe (134,000 mg/L), overcoming many other extreme cases of AMD pollution. The Ficklin diagram exposes that most samples are classified as “high-acid, high-metal.” Two of them have extreme classifications (high-acid, extreme-metal). The pH value is well below the acceptable range for the environmental quality of superficial waters (5–7), measuring at a minimum of 0.84. Regarding seasonal variability, the study showed a higher degree of contamination in dry conditions (e.g., 4,420 mg/L of Cu), while the rainy month had lower concentrations of PTE (186.8 mg/L of Cu for the same sampling point). In addition, the water does not accomplish the environmental objectives established by the EU Water Framework Directive. According to the new approach developed based on a scale adjustment, the potential ecological risk index studied indicates that most sampled sites present strong, very strong, and even extremely potential ecological risk. With a typical Mediterranean climate, the region suffers from water scarcity, predicting increasingly in the future more degrading scenarios for water environmental quality. Consequently, urgent mitigation and remediation measures are necessary to improve and preserve water quality and fulfill the objectives of the United Nations Sustainability Development Goals.