Mesoporous Li4Ti5O12 is prepared via ball-milling assisted solid-state reaction with titanyl sulfate and LiOH as precursors. Different from previous reports, the solid-state reaction route generates mesopores in Li4Ti5O12 by removing the impurities after the high-temperature synthesis process. This technique ensures the formation of well-defined mesoporous structure and ultrafine nanoparticles with the size of around 8 nm. The as-prepared sample shows good rate and cycle performance. At the current density of 1750 mA g−1 (10 C), high initial discharge capacity of 174.5 mAh g−1 can be obtained, which can be retained at 143.4 mAh g−1 after 50 cycles. This facile ball-milling assisted solid-state reaction could be a practical way for the mass synthesis of mesoporous Li4Ti5O12 as high-performance anodes.