The coupled effects of frequent dynamic loading disturbances and inherent fractures within deep rock masses are recognized as key factors responsible for the instability of surrounding rock and the occurrence of dynamic disasters. To reveal the fatigue damage mechanism and energy-driven evolution characteristics of fractured rock masses under cyclic loading, uniaxial cyclic loading–unloading tests were conducted on sandstone specimens containing a single prefabricated fracture with different fracture inclination angles (0°~90°) and stress amplitudes (20%σ?~80%σ?). The results indicate that the effective load-bearing cross-section and the macroscopic failure mechanism are predominantly governed by the fracture inclination angle. The peak strength was found to increase monotonically with increasing fracture inclination angle, while the overall failure pattern was characterized by tensile splitting dominated by wing-crack propagation. A significant non-monotonic influence of cyclic stress amplitude on the mechanical response of the rock was observed. At low and medium stress amplitudes, microcracks and pores were compacted, resulting in a fatigue-hardening effect, whereas fatigue creep was induced at high stress amplitudes, leading to stiffness degradation and increased plastic deformation. The evolution of energy dissipation exhibited a typical "L-shaped" trend, characterized by high initial dissipation, rapid attenuation, and a prolonged stable stage. Before the onset of critical instability, specimens with high fracture inclination angles were capable of storing a large amount of releasable elastic strain energy, making sudden and severe brittle failure more likely to occur upon failure. Based on the elastic modulus and cumulative dissipated energy, a generalized cumulative damage variable Dn was established. The exponential accumulation of internal dissipated energy under high-stress conditions was quantitatively characterized by this variable, and the nonlinear acceleration of fatigue damage evolution was accurately captured. The findings provide a deeper understanding of the fatigue deterioration mechanism of fractured rock masses and offer a scientific basis and data support for safety assessment and the early warning of dynamic disasters in deep underground engineering.