The potential risk from cyanobacteria blooms is the basis for predicting, preventing, and managing eutrophication. Poyang Lake lies on the southern bank of the middle and lower reaches of the Yangtze River. This lake is a large shallow lake connected to the Yangtze River and is affected by monsoon. The comprehensive evaluation index system, evaluation model, and method of the potential risk from cyanobacteria blooms were constructed based on the nutrient zoning in Poyang Lake, and the potential risk from cyanobacteria blooms was evaluated in 2013. (1) The evaluation index system comprises physical, chemical, and biological indicators. The physical indicators consist of blocking degree, lake region location, transparency (Secchi disk depth, SD), and temperature; the chemical indicators consist of total nitrogen (TN) and total phosphorus (TP); and the biological indicators consist of chlorophyll a (Chla) and phytoplankton biomass. Among the indicators, blocking degree and lake region location along with the prevailing wind direction were selected to represent the indicators affected by water retention time and wind direction. (2) We established a comprehensive evaluation method for assessing the potential risk from cyanobacteria blooms by adopting both analytic hierarchy process weighting and a comprehensive evaluation method. (3) Results show that the high-risk periods for cyanobacteria blooms were August, July, and December, and the high-risk regions were in the Northeastern Lake Region, Western Lake Region and Northern Lake Region. The Northeastern Lake Region is particularly in high risk in August and July. These cyanobacteria blooms presented heavy risk or close to heavy risk. Based on the risk evaluation indicators, outbreaks of cyanobacteria blooms are limited by temperature and location. Chla and phytoplankton biomass were the key indices affecting the level of potential risk from cyanobacteria blooms during the high-water-level period (July and August). In contrast, TN and TP are the key indices affecting the level of harm during the low-water-level period. Within a year, Chla, phytoplankton biomass, and TP are key indicators for the prediction of cyanobacteria blooms in Poyang Lake.