Abstract Undesired biofouling processes severely compromise the performance and durability of materials, including those used in biomedical and marine environments, strongly demanding effective and robust antifouling coating strategies. This paper presents the design, synthesis, and application of a highly water‐soluble zwitterionic monomer, carboxybetaine methacryloyl ethylenediamine (CB‐MAEDA), in the fabrication of ultralow‐biofouling polymer brushes via surface‐initiated, activators regenerated by electron transfer atom transfer radical polymerization (SI‐ARGET ATRP). CB‐MAEDA is synthesized through a reproducible, high‐yield (>80%) route, and its surface‐initiated polymerization under ambient aqueous conditions produces uniform poly(CB‐MAEDA) brushes, which achieve a 96.5% reduction in Escherichia coli adhesion. Collectively, these results demonstrate that SI‐ARGET ATRP of CB‐MAEDA affords thick, highly hydrophilic, and exceptionally effective antifouling coatings, underscoring its potential as a versatile platform for interface engineering in biomedical and related applications.