The direct synthesis of an acid-labile polyphosphoramidate by organobase-catalyzed ring-opening polymerization and an overall two-step preparation of polyphosphodiester ionomers (PPEI) by acid-assisted cleavage of the phosphoramidate bonds along the backbone of the polyphosphoramidate were developed in this study. The ultrafast organobase-catalyzed ring-opening polymerization of a cyclic phospholane methoxyethyl amidate monomer initiated by benzyl alcohol allowed for the preparation of well-defined polyphosphoramidates (PPA) with predictable molecular weights, narrow molecular weight distributions (PDI < 1.10), and well-defined chain ends. Cleavage of the acid-labile phosphoramidate bonds on the polyphosphoramidate repeat units was evaluated under acidic conditions over a pH range of 1-5, and the complete hydrolysis produced polyphosphodiesters. The thermal properties of the resulting polyphosphoester ionomer acid and polyphosphoester ionomer sodium salt exhibited significant thermal stability. The parent PPA and both forms of the PPEIs showed low cytotoxicities toward HeLa cells and RAW 264.7 mouse macrophage cells. The synthetic methodology developed here has enriched the family of water-soluble polymers prepared by rapid and convenient organobase-catalyzed ring-opening polymerizations and straightforward chemical medication reactions, which are designed to be hydrolytically degradable and have promise for numerous biomedical and other applications.