The shallow weathering fissure groundwater in the red-bed area of Southwest China is usually the only drinking water source for most rural residents. In this study, a typical landfill with surrounding residents drinking unpurified groundwater in red-bed area was selected and water quality detection, groundwater numerical simulation and human health risk assessment were used to identify and assess groundwater pollution in the region. The chemical type evolved from HCO3-SO4-Ca-Mg and HCO3-SO4-Ca to Na-Ca-Cl-HCO3 contaminated by the landfill. Na+ and Cl− were selected as factors for rapid identification of groundwater pollution. Subsequent analyses using these factors showed that the leachate pollution plume boundary was 190 m downstream of the landfill. Analysis of the redox conditions revealed that the area from the landfill to 5 m downstream was the reduction zone, while the area beyond 5 m was the oxidation zone. The migration and attenuation patterns of inorganic salts (such as SO42−) and heavy metals (such as Fe and Mn) in the oxidation and reduction zones differed obviously. Meanwhile, the organic pollutants in the leachate were reduced and decomposed into organic acids, which caused the groundwater 80 m downstream of the landfill to become weakly acidic (pH ranged from 6.51 to 6.83), and promoted re-entry of adsorbed heavy metals (such as Pb) into the groundwater. The groundwater risk assessment based on human health revealed that lead, manganese, chlorobenzene, dichloroethane and chloroform constituted a major health threat to the residents. The rank of non-carcinogenic risk was lead >manganese, and the maximum area of non-carcinogenic risk was 15,485 m2. The total carcinogenic risk caused by organic pollutants was 7.9 × 10−6, and the area of the carcinogenic risk zone was 11,414 m2. Overall, the results of this study provide a scientific basis for management of drinking water and groundwater remediation in the red-bed area with low permeability.