A catalytic hydrolysis rate of nerve agents can be a significant issue because of their severe toxicity which can lead to severe damage to human life. Regarding the issue, much effort has been given rise to the development of the various design of Zr(IV)-based MOF catalysts so that high catalytic performance. However, we still have feasibility issues. To this end, we turned our attention to develop the method for facile, scalable, and efficient synthesis of Zr(IV)-based MOFs (UiO-66) with high-performance hydrolysis by imparting enriched active sites to the catalysts, as well as to examine its feasibility using the combination of Ui0-66 with the organic bases including 4-ethylmorpholine (4-EM) and linear-/ branch-type polyethyleneimine (PEI). The modulated UiO-66 catalysts were synthesized by varying the total reaction concentration. The synthesized three different UiO-66 catalysts were characterized and then applied for hydrolysis rates of the methylparaoxon (MPO) nerve agent simulant. From these investigations, we found that the highest concentration led to the smallest particle size (ca. 100 nm) and highest defect density (1.8 per cluster), resulting in 3-times higher catalytic activity (0.548 s(-1)) in turnover frequency (TOF) relative to that of the uncontrolled UiO-66 (ca. 580 nm and 1.6 per cluster) (0.188 (-1)) which is prepared by the reported procedure. In addition, the reaction process significantly influenced on the catalytic activity of UiO-66, in which the simple change of the reagent mixing method led to a ca. 182-times difference in the catalytic activity for MPO hydrolysis despite using the same reagents including catalysts and bases. Importantly, we found that the reaction process-dependent catalytic activity of UiO-66 can be significantly associated with the chelation of Zr(IV) Lewis acidic active sites by base materials of 4-EM and PEI (Lewis base). Furthermore, the solid-state catalytic system based on the polymer composite of Ui0-66S/LPEI Ok on the cotton fabric was also examined for MPO hydrolysis at various relative humidity and temperature conditions to create actual atmosphere conditions, which gave the possibility for actual military applications such as protective suits and equipment. In addition, we schematically demonstrated the loss of active sites on Ui0-66 by chelation effects based on experimental and density functional theory (DFT)-derived computational simulation because it is highly correlated to the feasibility of Zr(IV)-based MOF catalysts for detoxification of nerve agents. In addition, we carefully propose a plausible reaction mechanism step on the nucleophilic attack by hydroxide group on the basis of the computational simulation.