Groundwater pollution by nitrate has is a major concern in the Tehran–Karaj aquifer, Iran, where the wells provide up to 80% of the water supply for a population of more than 18 million—yet detailed human health risks associated with nitrate are unknown due to the lack of accessible data to adequately cover the aquifer in both place and time. Here, using a rich dataset measured annually in more than 75 wells, we mapped the non-carcinogenic risk of nitrate in the aquifer between 2007 and 2018, a window with the most extensive anthropogenic activities in this region. Nitrate concentration varied from ~ 6 to ~ 150 mg/L, around three times greater than the standard level for drinking use, i.e. 50 mg/L. Samples with a non-carcinogenic risk of nitrate, which mainly located in the eastern parts of the study region, threatened children’s health, the most vulnerable age group, in almost all of the years during the study period. Our findings revealed that the number of samples with a positive risk of nitrate for adults decreased in the aquifer from 2007 (17 wells) to 2018 (6 wells). Although we hypothesized that unsustainable agricultural practices, the growing population, and increased industrial activities could have increased the nitrate level in the Tehran-Karaj aquifer, improved sanitation infrastructures helped to prevent the intensification of nitrate pollution in the aquifer during the study period. Our compilation of annually mapped non-carcinogenic risks of nitrate is beneficial for local authorities to understand the high-risk zones in the aquifer and for the formulation of policy actions to protect the human health of people who use groundwater for drinking and other purposes in this densely populated region.