The aim of this work was to determine the concentrations, distribution, and fate of potentially toxic elements [lead (Pb), zinc (Zn), nickel (Ni), copper (Cu), mercury (Hg), arsenic (As), and cadmium (Cd)] in sediments of a hydropower plant water reservoir located in the Brazilian Cerrado biome (used as system model). The purpose of this study was achieved with an analysis of the level of contamination based on the geoaccumulation index (Igeo) and factor contamination (FC) and comparisons with values established by environmental legislation. The physical–chemical–biological properties of sediment samples, the distribution, and the fate of potentially toxic elements (PTEs) in the basin of the stream studied were also investigated using Pearson’s correlation coefficient (r) and principal component analysis (PCA). Cu, Hg, and Cd concentrations in the sediment samples from most of the points analyzed were above level II of the categorization stipulated in environmental legislation, characterizing sediments of poor quality. Moreover, Igeo and FC values indicated potential pollution of the water reservoir sediment by Cd. Concentrations of Cd exceeding 0.34 mg kg−1 surpassed the reference values for water quality established by Conama Resolution No. 454/2012, highlighting the urgent need for ongoing sediment quality monitoring strategies. Hence, the study water reservoir was classified as being moderately to extremely polluted due to the fate of potentially toxic metals in the sediment samples. Frequent monitoring of the sediment quality in watersheds with hydropower plants is indispensable for the assessment of water resources, considering the importance of the water supply and power generation for the population. Moreover, water contaminated by PTEs poses potential risks to river basins, as well as to human and animal health. The results of this work can assist in the investigation of other water reservoirs around the world.