The process of water quality testing is money/-time-consuming, quite important and difficult stage for routine measurements. Therefore, use of models has become commonplace in simulating water quality. In this study, the coactive neuro-fuzzy inference system (CAN-FIS) was used to simulate groundwater quality. Further, geographic information system (GIS) was used as the preprocessor and post-processor tool to demonstrate spatial variation of groundwater quality. All important factors were quantified and groundwater quality index (GWQI) was developed. The proposed model was trained and validated by taking a case study of Mazandaran Plain located in northern part of Iran. The factors affecting groundwater quality were the input variables for the simulation, whereas GWQI index was the output. The developed model was validated to simulate groundwater quality. Network validation was performed via comparison between the estimated and actual GWQI values. In GIS, the study area was separated to raster format in the pixel dimensions of 1 km and also by incorporation of input data layers of the Fuzzy Network-CANFIS model; the geo-referenced layers of the effective factors in groundwater quality were earned. Therefore, numeric values of each pixel with geographical coordinates were entered to the Fuzzy Network-CANFIS model and thus simulation of groundwater quality was accessed in the study area. Finally, the simulated GWQI indices using the Fuzzy Network-CANFIS model were entered into GIS, and hence groundwater quality map (raster layer) based on the results of the network simulation was earned. The study's results confirm the high efficiency of incorporation of neuro-fuzzy techniques and GIS. It is also worth noting that the general quality of the groundwater in the most studied plain is fairly low.