Ti2Nb10O29 has recently been reported as a promising anode material for lithium-ion batteries. However, its poor electronic conductivity and insufficient Li+-ion diffusion coefficient significantly limit its rate capability. To tackle this issue, a strategy combining nanosizing and crystal-structure modification is employed. Ti2Nb10O29–x mesoporous microspheres with a sphere-size range of 0.5–4 μm are prepared by a one-step solvothermal method followed by thermal treatment in N2. These Ti2Nb10O29–x mesoporous microspheres exhibit primary nanoparticles, a large specific surface area (22.9 m2 g−1) and suitable pore sizes, leading to easy electron/Li+-ion transport and good interfacial reactivity. Ti2Nb10O29–x shows a defective shear ReO3 crystal structure with O2− vacancies and an increased unit cell volume, resulting in its increased Li+-ion diffusion coefficient. Besides Ti4+ and Nb5+ ions, Ti2Nb10O29–x comprises Nb4+ ions with unpaired 4d electrons, which significantly increase its electronic conductivity. As a result of these improvements, the Ti2Nb10O29–x mesoporous microspheres reveal superior electrochemical performances in term of large reversible specific capacity (309 mAh g−1 at 0.1 C), outstanding rate capability (235 mAh g−1 at 40 C) and durable cyclic stability (capacity retention of 92.1% over 100 cycles at 10 C).