As a response to climate changes, permafrost has deteriorated and the hydrologic process has undergone significant alterations in high-cold regions. The response mechanism still remains unknown. The characteristic contribution was calculated using the random forest (RF) algorithm, AdaBoost algorithm, and gradient-boosted decision tree (GBDT) algorithm. A comprehensive evaluation model was constructed to evaluate the contribution of climate changes to the headwaters of the Yellow River and the influence of permafrost degradation as well as climate-permafrost cooperation on runoff changes. The selected characteristic vectors were chosen as datasets for the support vector machine (SVM) and RF algorithms. A model was constructed for the prediction of permafrost degradation and runoff changes based on climate data. Results demonstrated that climate variables influencing the mean depth-to-permafrost table (DPT) were ranked according to their contributions: air temperature > evapotranspiration > wind speed > relative humidity (RHU) > sunshine duration > precipitation. The descending rank of climate and permafrost variables according to their contributions to runoff was the following: precipitation > sunshine duration > permafrost coverage > evapotranspiration > relative humidity (RHU) > mean DPT > wind speed > maximum DPT > air temperature. The model demonstrated good prediction results. The outputs can provide scientific references in applications related to water resources and the protection of ecologically vulnerable areas in high-cold regions.