Azirinyl ethynyl ketones, containing aryl/n-alkyl substituents at azirine C2/C3 and aryl/n-alkyl/2-thienyl substituents at the C≡C triple bond, undergo isomerization into 5-alkynyloxazoles under nucleophilic assistance in MeOH–K2CO3 media at room temperature, with the formation of 5-alkynyloxazoles in 20–84% yield. According to DFT calculations, the addition of the methoxide anion nucleophile to the C=N bond of azirine promotes the opening of the three-membered ring across the C–C bond. The subsequent 5-endo-trig cyclization of formed 2-azabuta-1,3-dien-4-olate and aromatization results in the formation of the alkynyloxazole derivative.