In this study, the mechanism of thermal exposure on the mechanical properties of two Ti60 alloys with different micro-texture regions (MTRs) was systematically investigated through macro- and microstructural characterization. It was found that when the alloy was exposed to prolonged thermal exposure at 600 °C for 100 h, the strength of the no-MTR samples increased significantly and the plasticity decreased sharply. In contrast, the MTR samples showed a sharp decrease in strength and plasticity due to the transmissibility of dislocation slip and crack propagation, resulting in the formation of a continuous brittle cleavage plane on the fracture. Meanwhile, the oxide film formed on the surface promotes the formation of early cracks and cleavage planes, and the oxide film serves as the location of surface crack nuclei and creates a notch effect leading to premature fracture of the alloy. It is further found that the oxide film is mainly composed of alternating nanocrystalline grains of Al2O3 and TiO2, and there is an oxygen-rich layer of Ti3O near the matrix, and these nano-oxides increased the brittleness of the oxide film. The strengthening and embrittlement mechanism of the alloy was revealed based on the deformation characteristics, i.e. the plasticity reduction was attributed to the formation of the oxide film and precipitation of the α2 phase on the surface, whereas the inhomogeneous distribution of the α2 phase in the interior led to the formation of microcracks in the interior. The precipitation of (Ti, Zr)6Si3 phase at grain boundaries hinders the dislocation motion and leads to a significant increase in the strength of No-MTR alloys. This study reveals the effects of interactions between MTRs, oxide films and precipitated phases on the thermal exposure properties of Ti60 alloys, providing theoretical support for the stability of titanium alloy properties at elevated temperatures.