We report here the first inventory of mercury (Hg) contamination in the region of Kedougou, Senegal, where mercury (Hg) is used for gold amalgamation in artisanal small-scale gold mining (ASGM) activities. Sediment cores were sampled during the dry and wet seasons, and at different locations along the Gambia River in the Kedougou region to evaluate the spatio-temporal trends of Hg distribution related to ASGM activities. The sediment samples were analyzed for total mercury and trace element concentrations (Cr, Cu, Zn, Pb, As, and Sc). The results highlight high concentrations of total Hg (reaching up to 9.9 mg.kg-1) in sediment cores sampled in the vicinity of ASGM operations, with the highest values reported for the dry season. The calculation of the Hg Enrichment Factor (EF) using Sc as refractory element, confirm high enrichments around active sites of gold mining being proportional to the density of miners and the duration of mining activities. The Hg spatial distribution reveals a very local contamination and a limited downstream dispersion of the contaminant. The high Hg concentrations obtained at ASGM sites largely exceed the Sediment Quality Guidelines (SQGs) and the Probable effect concentration (PEC) for the Protection of Aquatic Life recommendation. Our results demonstrate that the ASGM activities discharged large amounts of Hg into the Gambia River ecosystem and that the accumulation of Hg in sediments may represent a significant human health risk and a potential source of toxicity for aquatic organisms.