There is continuous deterioration of freshwater systems globally due to excessive anthropogenic inputs, which severely affect important socio-economic and ecological services. We investigated the water and sediment quality at 10 sites along the severely modified Swartkops River system in the Eastern Cape Province of South Africa and then quantified the phytoremediation potential by native and non-native macrophyte species over a period of 6 months. We hypothesized that the presence of semi and permanent native and non-native macrophytes mats would reduce water and sediment contamination through assimilation downriver. Our results were variable and, thus, inconsistent with our hypotheses; there were no clear trends in water and sediment quality improvement along the Swartkops River. Although variable, the free-floating non-native macrophyte, Pontederia (=Eichhornia) crassipes recorded the highest assimilation potential of heavy metals in water (e.g., Fe and Cu) and sediments (e.g., Fe and Zn), followed by a submerged native macrophyte, Stuckenia pectinatus, and three native emergent species, Typha capensis, Cyperus sexangularis, and Phragmites australis. Pollution indices clearly showed the promising assimilation by native and non-native macrophytes species; however, the Swartkops River was heavily influenced by multiple non-point sources along the system, compromising the assimilation effect. Furthermore, we emphasise that excessive anthropogenic inputs compromise the system’s ability to assimilate heavy metals inputs leading to water quality deterioration.