Utilization of the nano-catalysts in synthesis of applicable heterocycles is a key focus of research in green chemistry. The present work describes a one-pot, three-component, simple, and efficient approach for the synthesis of a new series of N-bridged pyrido[1,2-a]pyrimidine candidates utilizing NiO-NPs as a green catalyst. α-Aminopyridine 1 was synthesized from one-pot condensation of 4-chlorobenzaldehyde, chloroacetyl chloride, and malononitrile in the presence of ammonium acetate. α-Aminopyridine 1 was condensed with a variety of aromatic or/heteroaromatic aldehydes and malononitrile in the presence of NiO-NPs to afford pyrido[1,2-a]pyrimidine derivatives in good yield (75–92%) and with simple purification. Mild reaction conditions, no-column purification, and high yield of the products are evident features of such an approach, in addition to the high efficiency, cheap, soft, chemically stable, and readily available NiO-NPs. The pyrido[1,2-a]pyrimidine fluorophores 3c,d, i, and 3j have higher fluorescence wavelengths at (λflu.max = 460–480 nm) than the rest of compounds 3a,b, and 3e–h (λflu.max = 430–455 nm).