Heavy metal pollution poses a serious threat to the environment and human health. Guizhou is a province with apparent regional features of heavy metal pollution such as lead, zinc, mercury, and arsenic in agriculture and mining soils. The coefficient of variation results showed that heavy metal pollution in the soils of agricultural planting areas and mine caves was closely related to human activities, and arsenic and zinc were greatly affected by human activities. In the water environment, mercury pollution presents in mine cave water samples, and cadmium, mercury, and lead pollution present in scenic park water samples. The results of single-factor pollution index showed that mercury in mine cave water samples and cadmium, mercury, and lead in scenic park water samples were graded as severe pollution. The results of Nemero pollution index showed the highest comprehensive pollution level of heavy metals was in scenic park water samples. In atmospheric dust fall, cadmium, mercury, lead are the most prominent pollution. Potential risks to ecological environment were identified for cadmium and mercury in all study areas and lead in other areas outside Wanshan. The results of integrated potential ecological risk index indicated a high-risk level of heavy metal pollution in atmospheric dust fall in the current study area. At present, the heavy metal pollutants in the environment of Guizhou are mainly originated from natural factors such as geological background content and soil-forming parent material, and human activities such as mining, metal smelting, agricultural activities, and sewage irrigation. The analysis showed serious heavy metal pollution in the environment of Guizhou, which caused harm to the local environment. It is crucial that environmental protection measures be taken during human activities.