Two-dimensional (2D) graphene oxide nanosheets serve as an excellent support material for immobilizing metal complexes to deal with the drawbacks of homogeneous catalysis. In this work, we report a magnetically retrievable graphene oxide (MGO) based copper nanocatalytic system that has been efficiently exploited for obtaining a series of pharmaceutically and biologically active benzoxazole scaffolds. The nanocatalyst was designed by covalent immobilization of dehydroacetic acid (DHA) onto a magnetic amino-silanized graphene oxide nanosupport which was accompanied by its metallation with copper acetate. The structure of the synthesized MGO hybrid material (Cu@DHA@APTES@MGO) was characterized by numerous physico-chemical techniques such as transmission electron microscopy (TEM), field emission scanning electron microscopy (FE-SEM), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), vibrating sample magnetometry (VSM), elemental mapping, atomic absorption spectroscopy (AAS), thermogravimetric analysis (TGA), Brunauer-Emmett-Teller (BET) surface area analysis and energy-dispersive X-ray fluorescence spectroscopy (ED-XRF). The fabricated architectures exhibited high efficiency for cyclization of 2-aminophenols and β-diketones with wide substrate scope, excellent functional group tolerance, a higher conversion percentage (>98%) and a high turnover number (TON). The exceptional catalytic activity could be attributed to the 2D architecture of graphene oxide which provides space for trapping of reactants between 2D graphitic overlayers and metal surfaces and the reaction proceeds to afford benzoxazole products with moderate to excellent conversion percentages. Notably, this nanocomposite could be recovered easily through an external magnetic force and reused for multiple runs without any appreciable loss in its catalytic efficacy.