The construction of controlled-release formulations improves the sustained-release performance and utilization efficiency of pesticides, which are important aspects in plant protection and environmental chemistry. The current study employs kasugamycin (Kas), which is widely used to control Magnaporthe oryzae, conjugated with carboxyl-functionalized ZnO quantum dots via amide linkages to yield a pH-responsive pesticide delivery system (Kas@ZnO). Physicochemical characterizations indicated the successful preparation of the Kas@ZnO nanoparticles. In vitro drug release assessments indicated that Kas@ZnO exhibited a loading capacity of 21.05% and could effect the controlled release of Kas in an acidic environment, which is beneficial given the unique acidic microenvironment of M. oryzae. Bioactivity assays demonstrated that Kas@ZnO could simultaneously inhibit mycelial growth and spore germination. Additionally, bioactivity tests showed that the control efficacy of Kas@ZnO against rice blast reached 67.43% after 14 days of in vivo spray inoculation, which was higher than that obtained with Kas (55.50%), suggesting improved beneficial effects of Kas@ZnO application over a prolonged duration. Moreover, Kas@ZnO enhanced the activity of defense-related enzymes in rice and upregulated the expression of defense-related genes, such as OsPR2, OsPR3, OsPR5, OsWRKY45, OsLYP6, and OsNAC4. Ultimately, the biosafety assessments revealed that Kas@ZnO did not exert any harmful effects on rice and demonstrated slight toxicity toward zebrafish. These findings indicate that Kas@ZnO can function as a pH-sensitive pesticide delivery system, allowing for targeted release of the pesticide within plant tissues. This technology demonstrates significant potential for eco-friendly plant disease management.