Groundwater serves an indispensable function in regions characterized by intensive agricultural activities, particularly within karst landscapes where the availability of surface water is markedly limited. In this research, an exemplar of a densely agricultural plain on Yungui Plateau is utilized to delve into the impact of agricultural activities on groundwater human health risk and water quality through detailed hydrogeochemical investigations. About 55.56% and 66.67% of groundwater samples are found to have NO3− and NH4+ contents exceeding the permissible limits for drinking purpose, respectively. Groundwater presents a trend of gradual evolution from HCO3-Ca type to Cl-Mg·Ca or Cl-Ca type along with increase of NO3− concentration. Water–rock interactions are the main natural factor that govern the groundwater hydrochemistry. Agricultural activities are the main causes of the enrichment of NO3− and salinity in groundwater. The potential non-carcinogenic risks for adult males, adult females, children and infants posed by toxic substances of NO3−, Fe, Mn, As and F are in the range of 0.317–9.836, 0.335–10.402, 0.342–10.598, and 0.584–18.114, respectively, and the main spread way is oral pathway. The health risks are mainly attributed by the excessive NO3− and As, which should be concerned in agricultural practices. EWQI value of groundwater is between 22.1 and 317.7, and only 33.33% of samples are suitable for direct drinking. Measures such as raising public awareness and selecting groundwater with good quality as the water supply source should be adopted to provide technical support for reducing anthropogenic pollution of groundwater in agricultural plains and protecting the health of residents.