We present a comprehensive study aimed to distinguish between natural and anthropogenic origin of some potentially toxic elements (PTEs: As, Cd, Cr, Cu, Pb, Sb, Sn and Zn) in soil, fine-grained sediment and suspended particulate matter (SPM) in the upper zone of the anthropogenically impacted Sava River (Slovenia, Croatia). The study area is also characterised by a diverse lithological composition and therefore has a wide range of geochemical compositions, which makes it quite challenging to determine the level of pollution in analysed materials. The local enrichment factors (LEFs) calculated for specific lithologies of the catchment such as Mesozoic carbonates, Neogene clastic sedimentary rocks as well as Paleozoic and Paleogene/Neogene siliciclastic rocks proved to be a good tool to reduce the grain-size effect and the signal of different provenances and finally to accurately identify the hotspots of pollution in the Sava catchment. For defined empirical functions, the LEFs of PTEs in background samples ranges: As (0.67–1.33), Cd (0.55–1.42), Cr (0.72–1.37), Cu (0.69–1.38), Pb (0.72–1.41), Sb (0.74–1.19), Sn (0.73–1.25) and Zn (0.73–1.42). There are still many sites impacted by past mining and smelting activities, but also untreated effluents with significant enrichment of Cd, Cu, Pb, Sb, Sn and Zn (LEFs range from 4 to 8; for the Voglajna River the LEF of Cd is ∼50 and of Zn ∼20) in the Sava zone and therefore require greater attention. This study improves our knowledge of the distinction between natural and anthropogenic sources of PTEs in sedimentary materials strongly influenced by different source lithologies that cause their contrasting geochemical signatures. •Geochemistry of soil, fine sediment and suspended matter in an urban river was studied.•Lithology caused great variability in geochemical composition of sedimentary materials.•Local enrichment factors were used to identify pollution sources.•Cd, Pb, Sb, Sn and Zn showed many exceedances of background levels.