MgH2 has attracted intensive interests as one of the most promising hydrogen storage materials. Nevertheless, the high desorption temperature, sluggish kinetics, and rapid capacity decay hamper its commercial application. Herein, 2D TiO2 nanosheets with abundant oxygen vacancies are used to fabricate a flower-like MgH2/TiO2 heterostructure with enhanced hydrogen storage performances. Particularly, the onset hydrogen desorption temperature of the MgH2/TiO2 heterostructure is lowered down to 180 °C (295 °C for blank MgH2). The initial desorption rate of MgH2/TiO2 reaches 2.116 wt% min−1 at 300 °C, 35 times of the blank MgH2 under the same conditions. Moreover, the capacity retention is as high as 98.5% after 100 cycles at 300 °C, remarkably higher than those of the previously reported MgH2-TiO2 composites. Both in situ HRTEM observations and ex situ XPS analyses confirm that the synergistic effects from multi-valance of Ti species, accelerated electron transportation caused by oxygen vacancies, formation of catalytic Mg-Ti oxides, and stabilized MgH2 NPs confined by TiO2 nanosheets contribute to the high stability and kinetically accelerated hydrogen storage performances of the composite. The strategy of using 2D substrates with abundant defects to support nano-sized energy storage materials to build heterostructure is therefore promising for the design of high-performance energy materials.