Large ZnO mesocrystals of hexagonal columnar morphology have been successfully synthesized by using liquid crystals (LCs) of cetyltrimethylammonium bromide (CTAB, CH3(CH2)15N+(CH3)3Br) as templates. The LC-templated growth process is established by monitoring the crystal morphology, phase evolution at various temperature stages for both ZnO building blocks and CTAB templates, where there is a phase transition and interaction between the two involved. In contrast to the well-studied mesocrystals derived from solutions, we propose a new formation scheme for the large mesocrystals, on the basis of our experimental observations using X-ray diffraction phase analysis, Fourier transform infrared, scanning electron microscopy, and transmission electron microscopy conducted at various stages of mesocrystal growth. The resultant mesocrystals are characterized by a level of mesoporosity and internal surfaces, where there is a large population of oxygen vacancies, as confirmed by their photoluminescence behavior.