Hydrological status and water table fluctuations are directly related to land use and/or land cover (LULC) changes in each area. In this research, the impact of LULC changes on groundwater quantity and quality of Khan-Mirza Plain, in the northern Karun watersheds, was investigated. For this purpose, Landsat 5, 7 and 8 satellite images and ETM and OLI sensors were employed to prepare the LULC map of Khan-Mirza Plain for 2006 and 2016 using the artificial neural network algorithm. The neural network algorithm with the general accuracy of 90/29 was classified into six use classes (agriculture, rangeland, residential areas, rocky and bare lands, gardens and lowlands). Analysis of changes indicated that agricultural and residential uses were increased, respectively, by 62.5% and 3.5%. The biggest change was in conversion of the rocky and bare lands for the agricultural use. Another change was in the LULC of rocky and bare lands and rangelands: these have been converted into to the residential areas. A few piezometric wells in the plain were also used to investigate the lowering of the groundwater table during the 2006- 2016 period. The quality parameters investigated were calcium, sodium, magnesium, potassium, all soluble solids, electrical conductivity, sulfate, chlorine, bicarbonate, and water acidity (PH). Investigation of the time variation of the groundwater quality parameters further showed that potassium, water acidity, and bicarbonate followed an upward trend during the studied time. Most chemical parameters of water had the highest concentrations in the central plain area. The results, therefore, showed that increase of degradation and growth of human activities in the region had both caused changes in the LULC, subsequently intensifying the quantitative and qualitative loss of groundwater in the Khan-Mirza Plain. Therefore, the areas with irrigated agriculture, dry farming, and undeveloped agriculture have been increased. One of the main reasons for lowering of water table in 2016 was the excessive exploitation of groundwater as a result of the change in agriculture uses.