The potential to utilise the free-floating macrophyte Pistia stratiotes L. to survey contamination of the Al-Sero Drain in the South Nile Delta, Egypt, by eight potentially toxic elements (PTEs) was investigated in this study. This study considered the absorption of eight PTEs (Cd, Co, Cu, Fe, Mn, Ni, Pb, and Zn), and the evaluated P. stratiotes were located in three sampling locations along the Al-Sero Drain, with sampling conducted in both monospecific and homogenous P. stratiotes. Samples of both types of P. stratiotes and water were collected on a monthly basis between May 2013 and April 2014 at each location, utilising three randomly chosen 0.5 × 0.5 m quadrats. Regression models were designed to predict the concentration of the PTEs within the plant’s shoot and root systems. Elevated water Fe levels were correlated with a rise in shoot system Fe concentration, whereas higher Ni concentrations in the water led to a higher Ni concentration within the root system. The latter was also true for Pb. Water Cu levels had a negative association with the Cu concentration within the P. stratiotes shoot system. Raised Fe levels were also correlated with a diminished Fe level within the roots. For all PTEs, P. stratiotes was characterised by a bioconcentration factor of more than 1.0, and for the majority by a translocation factor of less than 1.0. The goodness of fit for most of the designed models, as indicated by high R2 values and low mean averaged errors, demonstrated the associations between actual and predicted PTE concentrations. Any disparity between measured and predicted parameters failed to reach significance with Student t-tests, reinforcing the predictive abilities of the designed models. Thus, these novel models have potential value for the prediction of PTE uptake by P. stratiotes macrophytes inhabiting the Al-Sero Drain. Furthermore, the macrophyte’s constituents indicate the long-term impact of water contamination; this supports the potential future use of P. stratiotes for biomonitoring the majority of the PTEs evaluated in this study.