Nanobiocatalysts (NBCs) are an emerging innovation that paves the way toward sustainable and eco-friendly endeavors. In the quest for a robust and reusable nanobiocatalyst, herein, we report a nanobiocatalyst, namely CALB@MrGO, developed via immobilizing Candida antarctica lipase B onto the surface of Fe₃O₄-decorated reduced graphene oxide (MrGO). Next, the enormous potential of the NBC (CALB@MrGO) was checked by employing it to synthesize clinically important quinazolinone derivatives in good to excellent yield (70–95%) using differently substituted aryl aldehydes with 2-aminobenzamide. Further, the synthetic utility and generality of this protocol was proved by setting up a gram-scale reaction, which afforded the product in 87% yield. The green chemistry metrics calculated for the gram-scale reaction those prove the greenness of this protocol.