A series of functionalized sesamol–oxazine and quinoline–oxazine hybrids have been synthesized via one-pot reaction of sesamol/6-hydroxyquinoline, aromatic amines, and methanal. The structures of all the novel compounds were confirmed by spectral data. The structures of the synthesized hybrids were also confirmed by X-ray crystallographic studies. Mild reaction conditions, operational simplicity, short reaction times, simple workup, and high yields of products are salient features of this methodology.