Microcystins (MCs) produced by cyanobacteria pose a serious threat to public health. Intelligence on MCs distributions in freshwater is therefore critical for environmental agencies, water authorities, and public health organizations. We developed and validated an empirical model to quantify MCs in Lake Taihu during cyanobacterial bloom periods using the atmospherically Rayleigh-corrected moderate resolution imaging spectroradiometer (MODIS-Aqua) (Rrc) products and in situ data by means of chlorophyll a concentrations (Chla). First, robust relationships were constructed between MCs and Chla (r = 0.91; p < 0.001; t-test) and between Chla and a spectral index derived from Rrc (r = -0.86; p < 0.05; t-test). Then, a regional algorithm to analyze MCs in Lake Taihu was constructed by combining the two relationships. The model was validated and then applied to an 11-year series of MODIS-Aqua data to investigate the spatial and temporal distributions of MCs. MCs in the lake were markedly variable both spatially and temporally. Cyanobacterial bloom scums, temperature, wind, and light conditions probably affected the temporal and spatial distribution of MCs in Lake Taihu. The findings demonstrate that remote sensing reconnaissance in conjunction with in situ monitoring can greatly aid MCs assessment in freshwater.