Freshwater reservoirs are considered as the source of atmospheric greenhouse gas (GHG), but more than 96% of global reservoirs have never been monitored. Compared to the difficulty and high cost of field measurements, statistical models are a better choice to simulate the carbon emissions from reservoirs. In this study, two types of Artificial Neural Networks (ANNs), Back Propagation Neural Network (BPNN) and Generalized Regression Neural Network (GRNN), were used to predict carbon dioxide (CO 2 ) flux emissions from reservoirs based on the published data. Input variables, which were latitude, age, the potential net primary productivity, and mean depth, were selected by Spearman correlation analysis, and then the rationality of these inputs was proved by sensitivity analysis. Besides this, a Multiple Non-Linear Regression (MNLR) and a Multiple Linear Regression (MLR) were used for comparison with ANNs. The performance of models was assessed by statistical metrics both in training and testing phases. The results indicated that ANNs gave more accurate results than regression models and GRNN provided the best performance. With the help of this GRNN, the total CO 2 emitted by global reservoirs was estimated and possible CO 2 flux emissions from a planned reservoir was assessed, which illustrated the potential application of GRNN.