With increased clinical use of antibodies, long‐term delivery strategies are needed to decrease injection frequency and improve health outcomes. A three‐component drug‐delivery system was developed for competitive affinity release of a streptavidin–antibody conjugate from agarose–desthiobiotin hydrogels via controlled dissolution of sparingly soluble biotin derivatives. The antibody conjugate was localized in the hydrogel through streptavidin–desthiobiotin complexation. Dissolution of sparingly soluble biotin derivatives disrupts streptavidin–desthiobiotin complexation for controlled release of the antibody conjugate. Release was tuned by altering the total biotin derivative concentration without further hydrogel or antibody modification. First‐order tunable release of bioactive Avastin, a therapeutic anti‐VEGF antibody, was demonstrated from a non‐cytotoxic system for over 100 days.