The cyclic damage behavior of TC4 alloy, which is widely utilized in aerospace and other fields, is critical to the structural integrity of its components. The aim of this study is to elucidate the underlying microstructural damage mechanisms, from the aspect of microstructural evolution, slip activity, and dislocation configurations, during cyclic loading through advanced characterization techniques including EBSD and TEM. The results indicate an initial rapid hardening stage, during which strain is highly localized in microtextured regions due to deformation incompatibility with the surrounding grains. The material subsequently reaches a quasi-steady state, which is marked by accumulated plasticity. Influenced by crystallographic texture and loading direction, the pyramidal \left\{\mathrm{10}\overline{\mathrm{1}}\mathrm{1}\right\}<c + a> slip system exhibits the highest Schmid factor and is preferentially activated, dominating the deformation process and promoting a gradual grain reorientation toward the <\mathrm{11}\overline{\mathrm{2}}\mathrm{0}> direction. TEM analysis indicates that dislocations multiply and align parallel to α/β phase interfaces during cyclic deformation. These interfaces function as both dislocation sources and barriers, thereby enhancing the material's fatigue life. The synergistic coupling between dislocation activity at α/β interfaces and pronounced strain localization within microtextured regions is identified as the dominant mechanism governing cyclic deformation damage in TC4 alloy.