In this study, a survey for the spatial distribution of heavy metals in Chaohu Lake of China was conducted. Sixty-two surface water samples were collected from entire lake including three of its main river entrances. This is the first systematic report concerning the content, distribution, and origin of heavy metals (Cu, Cr, Cd, Hg, Zn, and Ni) in the Chaohu Lake water. The results showed that heavy metals (Cu, Cr, Zn, and Ni) concentrations in the estuary of Nanfei River were relatively higher than those in the other areas, while content of Hg is higher in the southeast lake than northwest lake. Moreover, Cd has locally concentration in the surface water from the entire Chaohu Lake. The heavy metal average concentrations, except Hg, were lower than the cutoff values for the first-grade water quality (China Environment Quality Standard) which was set as the highest standard to protect the social nature reserves. The Hg content is between the grades three and four water quality, and other heavy metals contents are higher than background values. The aquatic environment of Chaohu Lake has apparently been contaminated. Both the cluster analysis (CA) and correlation analysis provide information about the origin of heavy metals in the Lake. Our findings indicated that agricultural activities and adjacent plants chimneys may contribute the most to Cd and Hg contamination of Chaohu Lake, respectively.