Total organic carbon (TOC) is important geochemical data for evaluating the hydrocarbon generation potential of source rocks. TOC is commonly measured experimentally using cutting and core samples. The coring process and experimentation are always expensive and time-consuming. In this study, we evaluated the use of three machine learning (ML) models and two multiple regression models to predict TOC based on well logs. The well logs involved gamma rays (GR), deep resistivity (RT), density (DEN), acoustic waves (AC), and neutrons (CN). The ML models were developed based on random forest (RF), extreme learning machine (ELM), and back propagation neural network (BPNN). The source rock of Paleocene Yueguifeng Formation in Lishui−Jiaojiang Sag was taken as a case study. The number of TOC measurements used for training and testing were 50 and 27. All well logs and selected well logs (including AC, CN, and DEN) were used as inputs, respectively, for comparison. The performance of each model has been evaluated using different factors, including R2, MAE, MSE, and RMSE. The results suggest that using all well logs as input improved the TOC prediction accuracy, and the error was reduced by more than 30%. The accuracy comparison of ML and multiple regression models indicated the BPNN was the best, followed by RF and then multiple regression. The worst performance was observed in the ELM models. Considering the running time, the BPNN model has higher prediction accuracy but longer running time in small-sample regression prediction. The RF model can run faster while ensuring a certain prediction accuracy. This study confirmed the ability of ML models for estimating TOC using well logs data in the study area.