Clathrin-mediated vesicular formation and trafficking are responsible for molecular cargo transport and signal transduction among organelles. Our previous study showed that CHLOROPLAST VESICULATION(CV)-containing vesicles (CVVs) were generated from chloroplasts for chloroplast degradation under abiotic stress. Here, we show that CV interacts with the clathrin heavy chain (CHC) and induces vesicle budding towards the cytosol from the chloroplast inner envelope membrane. In the defective mutants of CHC2and the dynamin-encoding DRP1A, CVV budding and releasing from chloroplast is impeded. Genetically, the mutations of CHC2inhibit CV-induced chloroplast degradation and hypersensitivity to water stress. Moreover, CV-CHC2 interaction is impaired by the oxidized GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE (GAPC). GAPC1overexpression suppresses CV-mediated chloroplast degradation and hypersensitivity to water stress, while CVsilencing alleviates the hypersensitivity of gapc1gapc2plant to water stress. Together, our work reveals a previously-unknown pathway of clathrin-assisted CVV budding outwards from chloroplast, which is involved in chloroplast degradation and stress response.