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Designing effective management strategies for lake ecosystems requires an understanding of regional differences, interannual variability, and other drivers affecting the availability of nutrients to algae. In this study, generalized additive models (GAMs) based on meteorological factors and geographic location were developed to quantitatively estimate the availability of nutrients to algae (as represented by the ratio of Chlorophyll a (Chl a) to total phosphorus (TP) or total nitrogen (TN)) across 167 Chinese freshwater lakes and reservoirs. This model was then used to produce the first spatial and temporal estimates of Chl a/TP and Chl a/TN within mainland China from 1987 to 2016. The results revealed high spatial variability driven primarily by geographic location, which explained 58.86% of the observed variability in Chl a/TP (41.98% in Chl a/TN). In addition, high interannual variability was driven by annual average temperature for both Chl a/TP and Chl a/TN. These results point to a fundamental challenge in managing regions with high nutrient levels, because these regions also tend to exhibit the strongest interannual variability, such that the impact of changes in management practices will be modulated by meteorological variability. In addition, this study provides regionalization indicators that serve as a quantitative foundation for formulating nutrient ecoregions to better administer lakes and reservoirs in China. It is therefore imperative that models combining meteorological factors with geographic location are further developed to improve the simulation of spatio-temporal variability in the availability of nutrients to algae.