The Yenisei River, one of the largest rivers in the world, is contaminated with artificial radionuclides released by a Russian nuclear facility producing weapon-grade plutonium, which has been in operation for many years. Examination of Yenisei River sediment samples revealed the presence of artificial radionuclides typical of radioactive discharge from the Mining-and-Chemical- Combine (MCC) nuclear facility: isotopes of europium (152Eu, 154Eu, and 155Eu), cesium (137Cs and 134Cs), 60Co, 90Sr, and transuranium elements. The MCC is also a source of radioactive particles in the Yenisei. New data on radionuclide concentrations in sediments and radioactive particles in the Yenisei River were obtained using a wide range of analytical methods. Sequential extraction performed on samples of sediment cores showed different degrees of potential environmental availability of artificial radionuclides and uranium. In a few samples, 241Am was present in the unextractable form, which may be accounted for by the presence of microparticles of the reactor fuel. These microparticles were investigated using scanning electron microscopy, and their reactor origin was confirmed.