Crystalline layered silicates are promising materials for the rational design of innovative catalysts owing to their wide variety and easily tunable surfaces. However, diffusional limitation in their interlayer spaces limits their catalytic efficiency. Herein, we have developed a novel synthesis route to a highly active layered silicate catalyst utilizing Hiroshima University Silicates (HUSs). We attempted to tune the stacking structure of the silicate layers of HUS-2 and HUS-7 ion-exchanged with hexadecyltrimethylammonium (C16TMA) using organic-solvent treatment, and found that cyclohexane treatment of HUS-7 gave an aggregate of randomly restacked silicate nanosheets without degradation of the original silicate framework. We prepared amine-modified base catalysts by grafting with aminopropyltriethoxysilane, and investigated their catalytic performances in the transesterification of triacetin with methanol. The catalyst based on HUS-7 exhibited a much higher catalytic activity than that based on HUS-2 despite their similar framework topology. Moreover, the activity of the HUS-7-based catalyst was far superior to those of other base catalysts, such as amine-modified mesoporous silica, catalyst resin, and alkylamine. Detailed characterization of the catalysts revealed that the improved accessibility of reactant molecules to the immobilized functional units, which is derived from both the randomly stacked silicate layers and the bulky interlayer molecules incorporated, is the primary reason for the high catalytic efficiency of the layered silicate catalyst.