Heavy metal pollution caused by acid mine drainage (AMD) is a global environmental concern. The processes of migration and transformation of heavy metals carried by AMD are more complicated in karst areas where carbonate rocks are widely distributed. Water, suspended particulate matter (SPM), and sediments are the crucial media in which heavy metals migrate and it is important to elucidate the geochemical behavior of AMD heavy metals in these environments. This study tracked AMD heavy metals from release to migration and transformation in a natural river system in a karst mining area. AMD directly impacted the hydrochemical composition of the karst water environment, but the carbonate rock naturally neutralized the acidity of the AMD. AMD heavy metal concentrations decreased gradually after the tributaries from the mining area entered the main river, with the metals tending to accumulate in SPM and sediments. The forms in which heavy metals were present were influenced by pH and their relative concentrations. Raman spectroscopy and transmission electron microscopy of sediments from the mining area suggested that the presence of an iron phase plays an important role in the fate of AMD-derived heavy metals. It is, therefore, necessary to elucidate the mechanisms of iron phase precipitation from sediments in order to control AMD-derived heavy metals in karst mining areas. This study improves our understanding of the geochemical behavior of heavy metals in karst environments and provides direction for the prevention and control of AMD in affected areas.