In August 2021 (wet season), 45 sampling sites were established across the Poyang Lake area. The concentrations of Mn, Cu, Zn, Cd, Pb, Cr, As and Hg in the lake water were analyzed using Inductively Coupled Plasma Mass Spectrometry and Atomic Fluorescence Spectrometry. Human health risk assessment for heavy metals was conducted based on drinking water and dermal exposure parameters specific to the Chinese population. Spatial distribution characteristics of heavy metals and their associated health risks were analyzed using the Kriging interpolation method. Key results indicate: (1) The concentration of heavy metals in the study area ranged from 1.89 μg/L to 183.25 μg/L, with Mn exhibiting the highest average concentration and Cr the lowest. Elevated heavy metal concentrations were observed in the river-lake ecotone in the southern Poyang Lake, where Mn levels exceeded safety standards at the confluences of Poyang Lake with the Ganjiang, Xinjiang, and Fuhe rivers. (2) As and Cr posed significant human health risks in Poyang Lake. In 2021, carcinogenic risk dominated the heavy metal risks in the lake water, with As presenting a pronounced carcinogenic threat. Some sampling sites showed low non-carcinogenic risks for Cr. (3) High non-carcinogenic risk areas were primarily distributed in the southern lake region, while high carcinogenic risk areas were concentrated in the central lake region. Mn, As, and Cr are the heavy metals that need to be strictly controlled in Poyang Lake. The water pollution caused by heavy metals in the southern and central parts of the lake area should be given priority for prevention and control.