This study reports the first enzyme-mediated polymerization of dendritic macromonomers. The enzyme substrates are prepared by "click" conjugation between tyrosine and hydrophilic triethylene glycol (TrEG)-based dendrons of three generations (G1, G2, and G3). The resulting enzyme-polymerizable dendrons are defect-free as revealed by mass spectrometry, size-exclusion chromatography, and spectroscopic techniques. The phenol-containing macromonomers are water soluble and their polymerizations into dendronized polymers (denpols) are catalyzed by laccase (an oxidoreductase) under benign conditions (45 °C and aqueous medium at pH = 4.0) with copolymer yields between 30 and 40%. The resulting denpols consist of unnatural poly(tyrosine) backbones and dendritic poly(ether-ester) side chains and have molecular masses up to ∼13 000 Da (generation 1), ∼20 000 Da (generation 2), and ∼36 000 Da (generation 3) determined by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) analyses. They display amphiphilic properties and self-assemble in aqueous solutions to form aggregates with generation-dependent morphologies.