The heat generation rate (HGR) of lithium-ion batteries is crucial for the design of a battery thermal management system. Machine learning algorithms can effectively solve nonlinear problems and have been implemented in the state estimation and life prediction of batteries; however, limited research has been conducted on determining the battery HGR through machine learning. In this study, we employ three common machine learning algorithms, i.e., artificial neural network (ANN), support vector machine (SVM), and Gaussian process regression (GPR), to predict the battery HGR based on our experimental data, along with cases of interpolation and extrapolation. The results indicated the following: (1) the prediction accuracies for the interpolation cases were better than those of extrapolation, and the R2 values of interpolation were greater than 0.96; (2) after the discharge voltage was added as an input parameter, the prediction of the ANN was barely affected, whereas the performance of the SVM and GPR were improved; and (3) the ANN exhibited the best performance among the three algorithms. Accurate results can be obtained by using a single hidden layer and no more than 15 neurons without the additional input, where the R2 values were in the range of 0.89–1.00. Therefore, the ANN is preferable for predicting the HGR of lithium-ion batteries.