In metal–organic frameworks, confined space as a chemical nanoreactor is as important as organocatalysis or coordinatively unsaturated metal site catalysis. In the present study, a set of mixed-ligand structures with UiO-66 architecture have been prepared. To the best of our knowledge, for the first time, structures derived by the solvothermal mixing ligand method and ultrasonic-assisted linker exchange approaches have been compared. Additionally, the relationship between the preparation method, structural properties, and catalytic efficiency of the prepared materials in the Knoevenagel condensation of aldehydes has been investigated. The prepared catalyst is very stable and can be recovered and reused for at least ten periods.