Driver fatigue has become one of the major causes of traffic accidents, and is a complicated physiological process. However, there is no effective method to detect driving fatigue. Electroencephalography (EEG) signals are complex, unstable, and non-linear; non-linear analysis methods, such as entropy, maybe more appropriate. This study evaluates a combined entropy-based processing method of EEG data to detect driver fatigue. In this paper, 12 subjects were selected to take part in an experiment, obeying driving training in a virtual environment under the instruction of the operator. Four types of enthrones (spectrum entropy, approximate entropy, sample entropy and fuzzy entropy) were used to extract features for the purpose of driver fatigue detection. Electrode selection process and a support vector machine (SVM) classification algorithm were also proposed. The average recognition accuracy was 98.75%. Retrospective analysis of the EEG showed that the extracted features from electrodes T5, TP7, TP8 and FP1 may yield better performance. SVM classification algorithm using radial basis function as kernel function obtained better results. A combined entropy-based method demonstrates good classification performance for studying driver fatigue detection.