Ferroelectric mesocrystals of Bi0.5Na0.5TiO3 (BNT) with [100]-crystal-axis orientation were successfully prepared using a topotactic structural transformation process from a layered titanate H1.07Ti1.73O4·nH2O (HTO). The formation reactions of BNT mesocrystals in HTO-Bi2O3-Na2CO3 and HTO-TiO2-Bi2O3-Na2CO3 reaction systems and their nanostructures were studied by XRD, FE-SEM, TEM, SAED, and EDS, and the reaction mechanisms were given. The BNT mesocrystals are formed by a topotactic structural transformation mechanism in the HTO-Bi2O3-Na2CO3 reaction system and by a combination mechanism of the topotactic structural transformation and epitaxial crystal growth in the HTO-TiO2-Bi2O3-Na2CO3 reaction system, respectively. The BNT mesocrystals prepared by these methods are constructed from [100]-oriented BNT nanocrystals. Furthermore, these reaction systems were successfully applied to the fabrication of [100]-oriented BNT ferroelectric ceramic materials. A BNT ceramic material with a high degree of orientation, high relative density, and small grain size was achieved.