Driving fatigue seriously threatens traffic safety. In our work, the multifractal detrended fluctuation analysis (MF-DFA) method is proposed to detect driver fatigue caused by driving for a long time. First, the <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\theta $ </tex-math></inline-formula> (4 ~ 7 Hz) and <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\beta $ </tex-math></inline-formula> (14 ~ 32 Hz) subbands of subjects’ electroencephalogram (EEG) signals were extracted. Furthermore, the multifractal spectrum characteristic indexes, the fluctuation function, mass exponent, Hurst exponent, spectral width values, and symmetry, were analyzed. Finally, the characteristics of different driving states of subjects were compared and analyzed. The results show that there are significant differences in the Hurst exponent width values of the subjects’ EEG signals corresponding to different driving times, and the spectrum width values and symmetry of the multifractal spectrum. In addition, compared with several typical fatigue detection methods, the absolute value of the slope of the fit straight line for fatigue feature extraction by MF-DFA is larger. It means that the MF-DFA method is more effective in detecting driving fatigue.