Tannery wastewater (TWW) is a toxic and hazardous effluent that causes great harm to receiving ecosystems if released untreated. Here, magnesium oxide nanoparticles (MgO-NPs), synthesized from low-cost and readily available magnesite, were used for the treatment of real TWW under batch laboratory conditions. The optimum treatment conditions were 90 min contact time and 10 g MgO-NPs dosage per L of real TWW, under ambient pH and temperature. Results were underpinned by state-of-the-art analytical techniques, including ICP-OES, XRD, XRF, and FIB/EDS-SEM, along with geochemical modelling (PHREEQC). The removal efficiency for the main contaminants that are typically found in TWW was, from higher to lower score, Fe ≥ U ≥ Cr ≥ Mn ≥ Al ≥ Sb ≥ Cu ≥ Ni ≥ TOC ≥ COD≥ SO42−. The removal percentages for these contaminants were ≥99%, aside from Ni (97%), TOC (71%), COD (69%) and particularly SO42− (21%). The underlying mechanism for contaminants removal is linked to the scavenging of metals by the MgO-NPs, forming complexes, in combination with alkalinity addition (through MgO dissolution) that lead to contaminants precipitation. The PHREEQC geochemical model confirmed the existence of divalent, trivalent, oxyanions, and multivalent chemical species in MgO-NPs/TWW solution, including complexes. Contaminants attenuation was achieved through precipitation, co-precipitation, adsorption, and co-adsorption, while these were removed as hydroxides, sulfides, carbonates, oxide, and oxyhydrosulfates. Overall, results highlight the great potential of MgO-NPs for the sustainable management of real TWW. Display omitted •MgO nanoparticles were successfully used for real tannery wastewater treatment.•Optimum conditions for the treatment of tannery wastewater were determined.•PHREEQC geochemical model was used to complement experimental results.•The state-of-the-art analytical techniques were used to verify the fate of pollutants.