The causes of the changes in different heavy metals in the hypereutrophic Qilu Lake were investigated by reconstructing the change history of heavy metal contamination in the past century, combined with land-use change and meteorological data. The results indicated that Qilu Lake was one of the lakes with the most serious risk of heavy metal pollution in China. The potential ecological risk index (RI) has remained at a very high level, and Cd and Hg were the main ecological risk factors. Four types of the sedimental content profiles of the heavy metals were observed, i.e. increase (Cd, Pb, and As), decline (Fe, Al, Zn, Ni, and Cr), unchanged (Hg), and first increase and then decrease (Cu). The results suggested that Fe, Al, Zn, Ni, and Cr were mainly originated from natural sources, while Cd, Pb, As, Cu, and Hg were related to anthropogenic sources. The EF profiles of Cd, Pb, Hg, Cu, and As showed increasing trend implying that the anthropogenic input of those heavy metals was increasing. By analysis of the human activities in the catchment, the reduction of soil loss by interception effect of water conservancy facility development and the expansion of built-up land were the main causes for the decline in sedimental contents of Fe, Al, Zn, Ni, and Cr. The development of industry of ferrous metal smelting and manufacturing in recent decades may be the main sources of the anthropogenic heavy metals in Qilu Lake catchment. Additionally, the discharge of waste and fallouts from local cement plants and application of chemical fertilizers were possibly the main contributors of Cd and Pb. Long-distance atmospheric transportation from outside the catchment may also contribute to the enrichment of Hg in Qilu Lake. The results of this study provided insights for the management of heavy metal pollution in Qilu Lake catchment, as well as for the other lakes in Yunnan–Guizhou Plateau.