A nanocrystalline mesoporous CuO-ZnO hollow sphere was successfully fabricated by the hydrothermal method. The nanocomposite was formed in the presence of polyethylene glycol as a dispersant and D-glucose as a template. The mesoporous CuO-ZnO catalyst was further functionalized with benzenesulfonic acid to catalyze the esterification of palm fatty acid distillate (PFAD). The physicochemical, textural, structural, and thermal properties of the mesoporous CuO-ZnO mixed-oxide catalysts were evaluated. The modified mesoporous catalyst possessed unique textural properties. With a Cu/Zn atomic ratio of 1.0 the best catalytic activity through PFAD esterification was achieved. The optimum reaction conditions in terms of methanol/PFAD molar ratio, catalyst concentration, reaction temperature, and reaction time were determined.