Polymer sequence control is a challenging yet rewarding strategy to achieve enhanced material properties. The two major categories of sequence control include regiosequence and stereosequence. Here, we describe several catalyst-assisted sequence-controlled ring-opening polymerizations to construct polyesters with unprecedent properties.Alternating poly(lactic-co-glycolic acid) (PLGA) is reported to have linear degradation and reduced initial burst release for controlled drug delivery. We first report the synthesis of isotactic, alternating PLGA via a regioselective ring-opening polymerization of (S)-methyl glycolide (MeG). An enantiopure aluminum salen catalyst with binaphthyl backbone facilitates the regioselective ring-opening of this unsymmetrical cyclic diester exclusively at the glycolide acyl–oxygen bond. To better align with FDA-approved materials, we then develop the synthesis of syndioenriched, alternating PLGA from racemic MeG with an optimized racemic aluminum catalyst. Mechanistic studies are carried out to elucidate the pairing-enhanced catalyst regio- and stereocontrol. Polymer sequence fidelity has been established by NMR investigations, confirming a high degree of alternation of comonomer sequence and moderate syndiotacticity within the backbone stereoconfiguration. The resulting syndioenriched material is amorphous, which will facilitate drug complexation behavior. This living, chain-growth polymerization is able to reach low dispersities with tailored molecular weights. Stereocomplexation is a useful strategy for the enhancement of polymer properties by the co-crystallization of polymer strands with opposed chirality. Yet, with the exception of PLA, stereocomplexes of biodegradable polyesters are relatively underexplored and the relationship between polymer microstructure and stereocomplexation remains to be delineated, especially for copolymers comprised from two different chiral monomers. In this work, we prepared a series of polyesters from different combinations of racemic and enantiopure epoxides and anhydrides, via metal-catalyzed ring-opening copolymerization (ROCOP). Intriguingly, we found that only specific chiral combinations between the epoxide and anhydride building blocks result in the formation of semicrystalline polymers, with a single stereocenter inversion inducing a change from amorphous to semicrystalline copolymers. Stereocomplexes of the latter were prepared by mixing an equimolar amount of the two enantiomeric copolymers, yielding materials with increased melting temperatures compared to their enantiopure constituents. Following polymer structure optimization, the stereocomplex of one specific copolymer combination exhibits a particularly high melting temperature (Tm = 238 °C).