Coupling effects of fretting wear and cyclic stress could result in significant fatigue strength degradation, thus potentially causing unanticipated catastrophic fractures. The underlying mechanism of microstructural evolutions caused by fretting wear is ambiguous, which obstructs the understanding of fretting fatigue issues, and is unable to guarantee the reliability of structures for long-term operation. Here, fretting wear studies were performed to understand the microstructural evolution and oxidation behavior of an α/β titanium alloy up to 108 cycles. Contact surface degradation is mainly caused by surface oxidation and the generation of wear debris during fretting wear within the slip zone. The grain size in the topmost nanostructured layer could be refined to ∼40 nm. The grain refinement process involves the initial grain rotation, the formation of low angle grain boundary (LAGB; 2°–5°), the in-situ increments of the misorientation angle, and the final subdivision, which have been unraveled to feature the evolution in dislocation morphologies from slip lines to tangles and arrays. The formation of hetero microstructures regarding the nonequilibrium high angle grain boundary (HAGB) and dislocation arrays gives rise to more oxygen diffusion pathways in the topmost nanostructured layer, thus resulting in the formation of cracking interface to separate the oxidation zone and the adjoining nanostructured domain driven by tribological fatigue stress. Eventually, it facilitates surface degradation and the formation of catastrophic fractures.