In the present work, the specific surface area (BET), X-ray diffraction analyses (XRD), scanning electron microscopy (SEM) energy-dispersive X-ray analysis (EDS), and laser particle size analysis were employed in the investigation of mechanical activation mechanism of titanium-bearing blast furnace slag. The results indicated that the specific surface area of the activated slag was significantly larger than that of the unactivated slag. The reduced intensity of the (121), (202), (123) and (242) diffraction peaks, which belong to the perovskite (CaTiO3), stems mainly from the increase in the lattice distortion and the decrease in the unit-cell volume. Compared with the unactivated slag, the cumulative volume of medium particles (1 μm ≤ PS ≤ 100 μm) in the activated titanium-bearing blast furnace slag was significantly higher, which was suitable for the subsequent leaching process. With the increase of ball-to-material mass ratio, mechanical activation time, mechanical activation rotation rate, the activated titanium-bearing blast furnace slag were extensively bonded and agglomerated. According to the results obtained by XRD, BET, SEM and laser particle size analysis, we concluded that the optimum mechanical activation process parameters are ball-to-material mass ratio of 20:1, activation time of 170 min, and activation rotation rate of 400 min/r, respectively. We also concluded that mechanical activation mechanism of titanium-bearing blast furnace slag can be attributed to the increase of specific surface area, amorphization of mineral particles, enhanced strain, preferential dissolution of select crystal faces, structural disorder, change of microtopography, leading to more amenable to leaching process.