Accurate medium and long-term runoff forecasts play a vital role in guiding the rational exploitation of water resources and improving the overall efficiency of water resources use. Machine learning is becoming a common trend in time series forecasting research. Least squares support vector machine (LSSVM) and grey model (GM(1,1)) have received much attention in predicting rainfall and runoff in the last two years. “Decomposition-forecasting” has become one of the most important methods for forecasting time series data. Complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) decomposition method has powerful advantages in dealing with nonlinear data. Least squares support vector machine (LSSVM) has strong nonlinear fitting ability and good robustness. Gray model (GM(1,1)) can solve the problems of little historical data and low serial integrity and reliability. Based on their respective advantages, a combined CEEMDAN–LSSVM–GM(1,1) model was developed and applied to the runoff prediction of the lower Yellow River. To verify the reliability of the model, the prediction results were compared with the single LSSVM model, the CEEMDAN–LSSVM model and the CEEMDAN–support vector machines (SVM)–GM(1,1). The results show that the combined CEEMDAN–LSSVM–GM(1,1) model has a high accuracy and the prediction results are better than other models, which provides an effective prediction method for regional medium and long-term runoff prediction and has good application prospects.