Biocatalysis is promising for sustainable production of polymers. Enzyme-initiated reversible addition - fragmentation chain transfer (RAFT) polymerization is reported. Horseradish peroxidase (HRP) catalyzes oxidation of acetylacetone (ACAC) by hydrogen peroxide to generate ACAC radicals, which in the presence of a suitable chain transfer agent initiate efficient and well-controlled RAFT polymerization in aqueous buffer solution at room temperature. The versatility of HRP-initiated RAFT polymerization was demonstrated by controlled polymerization of a wide range of monomers, including both more and less activated monomers, under a variety of conditions, including both homogeneous solution polymerization and heterogeneous dispersion polymerization conditions. In all cases, the polymerization afforded excellent pseudo-first-order kinetics, predictable molecular weights, and narrow molecular weight distributions. Operation via RAFT mechanism of this HRP-initiated polymerization was confirmed by a combination of MALDI-ToF, NMR, and UV-vis as well as by chain extension to make well-defined block copolymers. The mildness, specificity, and biocompatibility of HRP-initiated RAFT polymerization were illustrated by controlled polymerization in undiluted fetal bovine serum (FBS) solution. RAFT polymerization initiated by glucose oxidase (GOx)-HRP enzymatic cascade catalysis was developed, opening up a new avenue to potential green synthesis of precision polymers by controlled radical polymerization in air.