We report herein a high-throughput methodology for the synthesis of 1,2,4-oxadiazole and 1,2,4-triazole small-molecule libraries using an integrated synthesis and purification platform. The heterocyclization relies first on a low-temperature peptide coupling of a diverse set of carboxylic acids and hydroxyamidines, hydrazonamides, or pyridyl hydrazides followed by a high-temperature cyclization to yield the respective heterocycles in a continuous flow process. The fully integrated synthesis and purification platform enables the rapid generation of chemical libraries, decreasing the drug discovery cycle time.