We report the synthesis, characterization, and degradation of a new type of functional poly(4-hydroxybutyrate) (P4HB). The polyesters were obtained via the Passerini multicomponent polymerization (MCP) of (E)-4-oxobut-2-enoic acid with two different isocyanides at room temperature and the subsequent hydrogenation. The trans-double bond in the monomer was designed to inhibit the formation of five-membered lactone and promote the polymerization. Two different side groups were incorporated into the side chains of the polyesters by varying the isocyanide component. All the polymers were thoroughly characterized by a variety of methods. Degradation of the polyester under acidic and neutral conditions was investigated by H-1 NMR and GPC. In both cases head-to-tail degradation via intramolecular cyclization by the attack of the hydroxyl end group to the ester carbonyl moiety occurred and yielded a nonacidic gamma-butyrolactone derivative as the single degradation product. On the basis of control experiments with small model compounds and other types of polyester, we proposed the degradation mechanism. In acidic condition, random scission of the ester group occurred simultaneously at a much slower rate than that of the head-to-tail degradation, while in neutral condition, random scission did not occur and the polymers degraded in a controllable unzipping depolymerization manner.