This study aimed at establishing the spatial and seasonal distribution patterns of dissolved metals, and assessing the water quality and potential human health risk, in rivers of Lake Chaohu Basin (LCB, China). Four seasonal samplings were conducted at 83 sites from April to December in 2018. The water quality was assessed using heavy metal evaluation index (HEI), while hazard index (HI) and carcinogenic risks indicated potential human risk, according to 12 metals (Cr, Mn, Fe, Ni, Cu, Zn, As, Mo, Cd, Sb, Ba, and Pb). Spatially, sites were effectively classified into Group I and II using cluster analysis. Generally, dissolved metals were low in rivers of LCB at whole basin scale. Total metals concentrations, as well as HEI and HI, were significantly higher in Group II compared with Group I. The mean total concentration was 496.38 μg L⁻¹, with the highest mean of Zn (233.39 μg L⁻¹), followed by Ba (170.66 μg L⁻¹). The pollution status was generally classified as “slightly affected” by HEI, with a mean of 1.51. According to HI, there were 6.02% and 10.84% of all the 83 sites (main in Nanfei River) with greater chances of harmful health risks for adults and children, respectively. Furthermore, a high risk was observed of Cr, As, and Ni, which was listed in the decreasing order. Although the dissolved metals were relatively low, the potential risk for human health still existed in rivers of LCB, which the local manager should pay more attention to in future.