The identity of heteroatoms within bioactive molecules can profoundly influence their physicochemical and biological properties. Evaluating heterocycle analogues featuring distinct heteroatoms for new therapeutic opportunities, however, often requires laborious de novo syntheses. Here we report a straightforward, two-step, one-pot strategy for the direct skeletal editing of readily available oxetanes into azetidines using a broad range of aromatic and aliphatic amines. This transformation proceeds under simple conditions through Lewis acid-mediated intermolecular aminolysis of oxetanes, followed by an intramolecular Mitsunobu-type dehydrative cyclization to forge the azetidine ring. The resulting non-redox skeletal editing platform features broad substrate scope, excellent functional group tolerance and compatibility with complex, drug-like molecules, enabling rapid access to azetidine analogues from oxetane precursors for heterocycle editing in drug discovery.