NaV2O5 mesocrystals were successfully synthesized from an alkaline-stripped pentavalent vanadium solution through a novel hydrothermal hydrogen reduction process. The optimal conditions for the hydrogen partial pressure, reaction temperature, initial solution pH value, and reaction time for the pure-phase NaV2O5 synthesis were ascertained to be 4 MPa, 200 °C, 4.0, and 2 h, respectively. The synthesis time (only 2 h) was greatly shortened, by nine times, compared with the most time-saving (18 h) hydrothermal process at present. X-ray diffraction (XRD) analysis revealed that the as-prepared powders demonstrated a typical layered orthorhombic structure of NaV2O5. The purity of the as-prepared NaV2O5 reached up to 99.98%. An electrochemical test showed that the as-prepared NaV2O5 has a potential application in sodium ion batteries. According to scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analyses, the as-prepared NaV2O5 powders were identified to have rod-like mesocrystals consisting of small rods which preferentially grow along the (010) direction. Furthermore, the phase transformation mechanism and crystal growth mechanism in NaV2O5 preparation were discussed systematically, based on which the synthesis mechanism of NaV2O5 was proposed as pentavalent vanadates pre-sedimentation, hydrogen reduction with dehydration, sodium ions insertion, and finally self-assembly oriented attachment. The synthesis process is characterized as time-saving and low-cost, and thus it may have great application prospects.