In this work, uniaxial fatigue tests combined with post-test X-ray computed tomography (CT) scanning were conducted on marble samples with different interbed orientations, in order to reveal the anisotropic damage evolution characteristics during rock failure. The dynamic elastic modulus, damping ratio, fatigue deformation, damage evolution, accumulative damage modeling and crack pattern were systematically analyzed. The testing results indicate that the interbed structure in marble affects the damage evolution and the associated dynamic mechanical behaviors. The damage curve in “S” style indicates three-stage trend, namely, initial damage stage, steady damage stage and the accelerated damage stage. The damage index during cyclic deformation for marble presents obvious discrepancy. In addition, a fatigue damage prediction models was employed numerically as double-term power equations based on the experimental data. It is found that the selected damage model is suitable in modeling the rapid damage growth in the early and final stage of rock fatigue lifetime. Moreover, post-test CT scanning further reveals the anisotropic damage characteristics of marble, the crack pattern in the fractured sample is controlled by the interbed structure. What is more, the most striking founding is that the fracture degree is in consistent with the damage accumulation within the steady damage stage. Through a series of damage mechanical behavior analysis, the internal mechanism of the effect of interbed orientation on damage evolution of marble is firstly documented.