A two-enzyme reaction sequence was utilized to generate phenolic polymers containing a thymidine pendent group. Thymidine was used as the model nucleoside and a trifluoroethyl ester derivative of p-hydroxyphenylacetic acid was used as the phenolic derivative. Regioselective acylation of thymidine at the 5′-hydroxyl was achieved in nearly anhydrous CH3CN using the lipase from Candida antarctica. This was followed by the polymerization of the phenolic nucleoside derivative catalyzed by the peroxidase from soybean hulls. A potential advantage of the coupled enzymatic approach is the high degree of control that can be exerted over both reactions that comprise the synthetic scheme for the generation of thymidine-containing polyphenols.