It is imperative to have an in-depth understanding of CO overrun at the air return corner not only for pre-warning concentrations of safety and spontaneous combustion but also for providing scientific guidance for the CO management. In this study, CO sources and early-warning concentration of spontaneous combustion at the air return corner in fully mechanized mining faces were investigated. Through field measurements, the main sources responsible for CO occurring at the air return corner of the fully mechanized mining face were determined and analyzed, and the basic parameters of mining and ventilation conditions were obtained from the field trials. In the laboratory, an enclosed reactor was introduced and a series of simulated experiments of coal oxidation was carried out to explore coal oxidation at ambient temperature; simultaneously, the temperature-programmed oxidation experiments were also carried out to determine the critical temperature of coal spontaneous combustion and to obtain the rate of CO production at a critical temperature. According to the analysis of the CO source and the production mechanism in the working face as well as both the distribution and migration rules of CO concentration in goaf and working face, a mathematical prediction model of the CO concentration at the air return corner of the working face under normal operation was established. And then the prediction of CO safety and spontaneous combustion early-warning concentrations were calculated based on the CO production rates of coal oxidation under ambient temperature and at a critical temperature. Moreover, a detailed operational process for the practical applications of the mathematical prediction model to the return corner of other fully mechanized mining faces was also proposed.