This study aimed to determine the effect of land-use changes on the non-carcinogenic health risk of nitrate ion exposure of underground drinking water resources in Shiraz (Iran). To this end, 175 chemical samples for the nitrate analysis were regularly taken from 35 drinking water wells of Shiraz from 2013 to 2017, and their results were zoned using GIS. Hazard quotient (HQ) induced by nitrate ion exposure was determined in four age groups: infants, children, adolescents, and adults. Area changes of four types of land-use, including residential, agricultural and green space, industrial, and bare land within a radius of 400 m of drinking water wells, were determined using the GIS and Google Earth software. Then, all data was imported to Matlab 2018 for statistical analysis. The results showed that mean nitrate concentration increased by 2.5 mg L −1 from 2013 to 2017. According to the zoning map, 5 and 11.4% of the area in 2013 and 2017, respectively, exceeded the drinking water standard set by nitrate (i.e., 50 mg/ L). Air temperature and precipitation variations also influenced nitrate concentrations and HQ changes (R temperature = 0.67). Children's age group was the most vulnerable, and during the study period, this vulnerability was an increasing trend, so that the HQ from 0.93 in 2013 to 0.97 in 2017 has increased. The rate of land-use changes in agricultural, industrial, bare, and urban was −1.8%, 1.3%, −4.6%, and 2.1%, respectively, and the highest correlation was observed between HQ and Diff.l residential land use (R infant = 0.55). According to the results, the most influential factor in HQ was air temperature (R = 0.66), and urban land-use change (R > 0.44). To sum up, this study's results showed that land-use changes, especially urban and residential development, significantly affect groundwater nitrate concentration and its degree of HQ. Moreover, increasing temperature and decreasing annual precipitation can also increase the severity of this risk.