Fouling-resistant coating materials have important applications in marine industry and biomedicine. Zwitterionic carboxybetaine polymers have demonstrated robust antibiofouling functionalities in experiments. In this work, we performed atomistic molecular dynamics simulations to study the molecular mechanism of hydration and antibiofouling of poly(carboxybetaine acrylamide) (polyCBAA) brush surfaces. We focused on the zwitterionic carboxybetaine, which has only a short methylene spacer between the positive quaternary ammonium and the negative carboxylate groups. Our study shows that a large amount of water is present within the polyCBAA surface, and a condensed water layer of single-molecular thickness covers the top of the polymer surface. Moreover, the clustering of the zwitterionic chains results in an amorphous structure of the polymer surface, a reduced degree of order in the interfacial water molecules, and weak protein attachment. The low protein desorption free energy demonstrates that the polyCBAA surface exhibits strong fouling resistance due to its significant interfacial hydration and the small dipole moment of the carboxybetaine group, minimizing protein-surface electrostatic interactions. Our study at the molecular level will be important to the future development of zwitterionic materials.