Large aggregate asphalt mixtures can absorb noise, reduce water damage, effectively improve the service life of roads, and reduce environmental pressure. In this study, the fatigue characteristics of a large-sized asphalt mixture, LSAM-30, were investigated using four-point bending tests. The fatigue performance of LSAM-30 was compared to that of AC-13 and AC-20 asphalt mixtures across a range of temperatures, frequencies, and strains. The results indicated that the temperature, frequency, and strain significantly affect the fatigue performance of LSAM-30. As the temperature or frequency increased, the disparity in the fatigue performances of LSAM-30, AC-13, and AC-20 became more pronounced. Furthermore, the variations in the strain did not exhibit a clear pattern in the fatigue performance ratio among the three asphalt mixtures, with the ratio changes being minor (<5%). Additionally, an exponential-function-based predictive equation was proposed, showing how the fatigue characteristics of LSAM-30 vary with changes in frequency and temperature.