The emergence of antibiotic resistance in riverine systems has become a growing issue worldwide. The use of watershed-scale models is popular with many other water quality issues but not in the case of antibiotic resistance. In this study, we introduce a watershed-scale bacteria fate and transport model to simulate antibiotic resistance in E. coli. This model was developed through amendments to an existing watershed-scale physically based hydrological model (SWAT), and the newly modified model was called SWAT-ARB. The SWAT-ARB model was employed in the receiving environment of a WWTP in the Adyar River basin, India. The SWAT-ARB model simulations of resistant fractions (resistant E. coli concentration/E. coli concentration) in stream water were analyzed by the flow levels with the application of a range of parameter values. It is concluded that the model can be used to test prevailing hypotheses and evaluate the current state of knowledge. For instance, model simulations suggest that the influx of ARB can be a primary driver of antibiotic resistance in rivers compared to ambient antibiotic concentrations. We used the SWAT-ARB model to quantify the impact of climate change on antibiotic resistance. Six climate models were used to obtain the future climates in two distinct scenarios. The model was applied to three watersheds as Adyar basin- India, Crab Creek basin- USA, and upper Viskan basin- Sweden. It was concluded that temperature increase may greatly affect the colder climates (Crab Creek and Viskan) with higher simulated resistant fractions. In case of Adyar basin, resistant fractions are alleviated in high flow conditions, while aggravated in low flow conditions.