Sediment samples from the Săsar River and its main tributaries were analyzed for their potentially toxic elements at the site of the Romplumb metallurgical company and near the well-known Pb-Zn-Cu epithermal deposit of Baia Sprie located in the Neogene volcanic chain of the Eastern Carpathians, Romania. The average metal concentrations arranged in order of decreasing abundance are as follows (mg·kg−1): Mn (4098) > Zn (2093) > Pb (918) > Cu (489) > As (160) > Cr (37.51) > Ni (30.25) > Co (28.13) > Cd (9.72) > Hg (1.81). Several pollution indices were successfully used to assess the degree of contamination and ecological risk. The majority of sampling sites indicate high degrees of pollution, with two major hotspots identified. There are further sources, such as the Șuior (Pb-Zn-Au) and Săsar (Au-Ag) epithermal deposits, Cuprom company, and Bozânta tailing ponds, identified as contaminants. The Baia Mare mining district is causing a serious threat to the aquatic systems in the region, and it can be taken as a reference area for the human impact derived from the mining of mineral deposits of Au-Ag-Cu-Pb-Zn. It is imperative to reduce ecological risks and thereby protect the population living within this abandoned mining area.