Recent years have witnessed noteworthy advancements in the designing of MOFs and their derived materials. The present work for the very first time reports the successful fabrication of a series of CuO nanoparticles (NPs) by the controlled pyrolysis of Cu-5-nitroisophthalate (Cu-NIPA) metal organic framework (MOF) and employed it further as a catalytic entity for accessing 2,3-dihydroquinazolinone moieties. The systematically designed CuO nanoarchitectures were synthesized in a single step through pyrolysis of Cu-5-NIPA in air atmosphere and analytically affirmed using a multitude of advanced physico-chemical characterization tools such as Fourier transform infrared (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), powder X-ray diffraction (PXRD), N2 adsorption-desorption isotherm, Raman spectroscopy and X-ray photoelectron spectroscopy (XPS) analysis. The catalytic potential of the developed CuO nanoarchitectures was subsequently evaluated in the one-pot multicomponent coupling of aromatic aldehyde, isatoic anhydride, alkyl/aryl amine to produce 2,3-dihydroquinazolinone scaffolds (up to 97% yield). Furthermore, a proposed catalytic mechanism for the concerned reaction has also been provided. Some of the additional startling attributes of the developed methodology include excellent product yield in short duration, easy work-up procedure, green reaction solvent, ambient reaction parameters, wide substrate scope, high turnover number and good recyclability for multiple runs.