A new empirical Chl-a algorithm has been developed and validated for the largest freshwater lake of China (Poyang Lake) using a normalized green-red difference index (NGRDI), where the uncertainty was estimated to be <45% for Chl-a ranging between 1.3 and 10.5 mg·m−3. The combined approach of using the NGRDI algorithm and atmospherically-corrected Medium Resolution Imaging Spectrometer (MERIS) data showed an advantage over other popular approaches. The algorithm was then applied to 325 carefully-selected MERIS full-resolution (300-m) scenes between 2003 and 2012, with pixels of extreme turbidity (NGRDI < 0.06, corresponding to >~25 mg·L−1 total suspended sediments or TSS) masked. The long-term Chl-a distribution showed significant spatial gradient and temporal variability, with Chl-a ranging between 2.4 ± 0.2 mg·m−3 in April and 4.4 ± 1.0 mg·m−3 in July and no significant increasing or decreasing trend during the 10-year period. In waters where Chl-a was retrievable (i.e., where TSS is 10 mg·m−3) in summer. The study not only provides, for the first time, synoptic baseline information on the lake’s Chl-a distributions and potential eutrophic regions, but also demonstrates a practical approach that might be extended to assess eutrophication conditions in other inland waters.