Abstract The potential ecological and human health risk of heavy metal pollution in sediment and Benthic Fauna (Chrysichthys auratus and Tympanotonus fuscatus) of Benin River, Southern Nigeria, was evaluated. Three sampling sites associated with heavy anthropogenic activities along the course of the river were sampled. Heavy metals concentrations were determined in the samples using atomic absorption spectrophotometer (Model 210 VGP, Buck Scientific). In all sediment samples, only Pb exceeded the threshold/probable effect level (TEL). Very high contamination degrees (CD > 24) 181.74, 50.11, and 101.96) for stations 1, 2, and 3, respectively, were observed indicating serious anthropogenic pollution. Geoaccumulation index (i geo) showed slight pollution with Pb and Cd and severely to extremely polluted with Fe across the stations. Cd exhibited moderate individual potential risk ($$E_{\text{r}}^{i}$$ Eri ), and the other heavy metals showed low $$E_{\text{r}}^{i}$$ Eri . Potential ecological risk index (RI) showed low risk of contamination for heavy metals in sediment. Human health risk assessment for Co, Cd, Cu, Zn, Mn, Fe, and Ni in C. auratus and Co, Zn, Mn, Fe, and Ni in T. fuscatus indicated no obvious health risk from these heavy metals over a lifetime of exposure. However, hazard quotient (HQ) values for Pb in C. auratus and Cd, Cu, and Pb in T. fuscatus indicated significant health risk. The hazard index (HI) values for both C. auratus and T. fuscatus were > 1 indicating significant adverse health risk of non-carcinogenic effect. Therefore, the consumption of these contaminated fish and shellfish by the people of Koko portends risks of the health of the public. The industries operating in this community should adopt more sustainable and eco-innovative management options in order to attenuate potential ecological and human health risk of metal pollution.