In the present study, a three-dimensional SEAWAT model was developed to generally simulate the impact of climate change and anthropogenic activities on seawater intrusion (SWI) in the coastal region of Benin by the end of 2050. The model was calibrated and validated from 2015 to 2020, considering groundwater head and salt concentration measured in 30 wells. After calibration, a sensitivity analysis was performed with the model parameters (hydraulic conductivity, recharge, storage coefficient and boundary conditions). For the calibration, model computed and observed values displayed good correlation, approximatively 0.82 with a root mean square error (RMSE) of 0.97 m and 13.38 mg/L for groundwater head and salt concentration, respectively. The simulation results indicate that freshwater head had declined by 1.65 m from 2015 to 2020 (taking reference from the average groundwater head in 2015: 27.08 m), while the seawater intrusion area increased in the same period by an average of 1.92 km2 (taking reference from the seawater intrusion area in 2015: 20.03 km2). The model is therefore used to predict groundwater level decline and seawater intrusion area increase by the end of 2050, considering the predicted sea level rise (SLR) and estimated groundwater pumping rate. Furthermore, the interface fresh groundwater–saltwater change was studied using the SHARP interface developed by USGS in 1990. The interface variation was found to be influenced by the distance from shoreline, sea level, groundwater level and geological formation hydraulic conductivity. Finally, the 3D model was used to simulate the effect of a managed aquifer recharge system on reducing SWI rate in the study region.