Antibiotic resistance genes (ARGs) emanating from wastewater treatment plants pose a potential risk to human health. Once the genes are in the receiving waters, they can decay but they can also be advected downstream far from the plant or through horizontal gene transfer, spread to native bacteria. A mathematical model is proposed with terms for advection, conjugation, transformation, net growth and segregation to predict for concentrations of antibiotic-susceptible bacteria and ARGs, both within bacteria and those that exist as free DNA.Simulations were compared to observed data for resistant and susceptible bacteria in the Upper Mississippi River. The data had previously been used with a transport-only model that served as the baseline for comparisons with this model. For resistant bacteria concentrations, there is a 2 to 7-fold improvement over the threshold root-mean-squared error of the transport-only model when biological processes are included, particularly decay. While the model predicted well for the resistant faction, the average predictions for susceptible bacteria concentrations were sometimes off by greater than an order of magnitude.