Carboxybetaine (CB)-based zwitterionic materials have attracted considerable attention due to their dual antifouling and functionalizable properties. In this communication, the elimination effect on the antifouling and pH-responsive properties of CB materials was investigated. We synthesize β- and α-substituted methyl CB materials to investigate the occurrence of elimination in the ethylene intercharge arm in a harsh basic solution. This work provides molecular understanding of a structure–property relationship of the CB moiety for material development.