Prediction of primary production of lentic water bodies (i.e., lakes and reservoirs) is valuable to researchers and resource managers alike, but is very rarely done at the global scale. With the development of remote sensing technologies, it is now feasible to gather large amounts of data across the world, including understudied and remote regions. To determine which factors were most important in explaining the variation of chlorophyll a (Chl-a), an indicator of primary production in water bodies, at global and regional scales, we first developed a geospatial database of 227 water bodies and watersheds with corresponding Chl-a, nutrient, hydrogeomorphic, and climate data. Then we used a generalized additive modeling approach and developed model selection criteria to select models that most parsimoniously related Chl-a to predictor variables for all 227 water bodies and for 51 lakes in the Laurentian Great Lakes region in the data set. Our best global model contained two hydrogeomorphic variables (water body surface area and the ratio of watershed to water body surface area) and a climate variable (average temperature in the warmest model selection criteria to select models that most parsimoniously related Chl-a to predictor variables quarter) and explained ~ 30% of variation in Chl-a. Our regional model contained one hydrogeomorphic variable (flow accumulation) and the same climate variable, but explained substantially more variation (58%). Our results indicate that a regional approach to watershed modeling may be more informative to predicting Chl-a, and that nearly a third of global variability in Chl-a may be explained using hydrogeomorphic and climate variables.