This article reports the cyclic deformation behavior of the b-annealed metastable Ti-5Al-5V-5Mo-3Cr (Ti-5553) alloy under the condition of pure compressive fatigue stress. The following three aspects, namely, the mechanical response, the surface morphology evolution, and the dislocation structures, were systematically investigated. Under all testing conditions, the material demonstrated cyclic softening in the initial cycles followed by saturation. The progressive observation of surface morphology at fixed locations, but after different numbers of cycles, elucidated typical planar slip behavior and the early appearance of fatigue microcracks, which were found often to be induced by the highly localized planar slip bands. The transmission electron microscopy (TEM) study revealed dislocation annihilation upon cycling, i.e., the reduction of dislocation density as well as the simplification of dislocation configurations. In addition, detwinning and changed twin boundary structures upon cycling were also detected. Such activities, together with the intersection of coherent x precipitates by moving dislocations, are considered to be responsible for the initial softening, whereas the dislocation dipole flip-flop mechanism is presumably responsible for the cyclic saturation behavior. An attempt was made to explain the strain-localized planar slip behavior by considering the stacking fault energy (SFE) as well as the free-electron-to-atom (e/a) ratio. The nanoscaled x and a precipitation in the b matrix may also contribute to the planar slip behavior. The effect of the microstructure in the as-received material was also analyzed for the strain localization and planar-slip mode.