To determine the nature and origin of the unconsolidated bottom sediments, as well as to demonstrate and quantify the presence of Presumably Contaminating Elements (PCE) in the Serbian Danube River, as a novelty, the mass fractions on nine major elements as oxides—SiO2, TiO2, Al2O3, FeO, MnO, MgO, CaO, Na2O, and K2O, as well as Sc, V, Cr, Co, Ni, Cu, Zn, As, Rb, Sr, Zr, Sb, Cs, Ba, La, Hf, Ta, W, Th, and U were determined by Instrumental Neutron Activation Analysis (INAA) in 13 sediment samples collected between Belgrade and Iron Gate 2 dam. INAA was chosen for its ability to perform elemental analysis without any preliminary sample treatment that could introduce systematic errors. The distribution of major elements was relatively uniform, with the sampling locations having less influence. Concerning the trace elements, excepting the PCE Cr, Ni, Cu, Zn, As, and Sb, their distributions presented the same remarkable similarity to the Upper Continental Crust (UCC), North American Shale Composite (NASC), Average Bottom Load (ABL), and Average Dobrogea Loess (AVL), and were in good concordance with the location of the Serbian Danube River in the Pannonian Plain. In the case of considered PCE, both Enrichment Factor and Pollution Load Index showed values higher than the pollution threshold, which pointed towards a significant anthropogenic contamination, and rising concern to what extent the water quality and biota could be affected.