Arsenic and mercury are potentially toxic elements of concern for soil, surficial and ground waters, and sediments. In this work various geochemical and hydrogeological tools were used to study a paradigmatic case of the combined effects of the abandonment of Hg- and As-rich waste on these environmental compartments. Continuous weathering of over 40years has promoted As and Hg soil pollution (thousands of ppm) in the surroundings of a former Hg mining-metallurgy site and affected the water quality of a nearby river and shallow groundwater. In particular, the high availability of As both in soils and waste was identified as one of the main determinants of contaminant distribution, whereas the impact of Hg was found to be minor, which is explained by lower mobility. Furthermore, potential additional sources of pollution (coal mining, high natural backgrounds, etc.) discharging into the study river were revealed less significant than the contaminants generated in the Hg-mining area. The transport and deposition of pollutants within the water cycle has also affected several kilometres downstream of the release areas and the chemistry of stream sediments. Overall, the environmental compartments studies held considerable concentrations of Hg and As, as remarkably revealed by the average contaminant load released in the river (several tons of As per year) and the accumulation of toxic elements in sediments (enrichment factors of As and Hg above 35).