2-Methylisoborneol (2-MIB) is a cyanobacterial metabolite that is responsible for many taste and odor (T&O) complaints related to the aesthetics of drinking water and poses a problem for water authorities because it is recalcitrant during conventional water treatment. A numerical model was developed to simulate 2-MIB in the Qingcaosha Reservoir, an estuarine drinking water resource in the Changjiang estuary with known 2-MIB episodes. The objective of this study was to numerically simulate the generation and release processes of 2-MIB in the reservoir and to provide useful information for better management of drinking water resources experiencing T&O problems caused by cyanobacteria. The simulation results from 2009 to 2013 showed that the simulated 2-MIB concentrations corresponded well to the observational data. 2-MIB was released mainly during periods of low dissolved oxygen (DO) levels with an adequate potential sediment source. The temporal and spatial variations in nutrients, chlorophyll-a (Chl-a), Cyanophyta and 2-MIB were presented and analyzed during 2009 to 2013. According to the study results, high-concentration areas and peak levels of 2-MIB can be controlled by inhibiting algal growth and increasing oxygen levels in the water, which can be achieved via adequate water exchange and oxygen exposure in the reservoir, respectively.