Based on disulfide-enriched multiblock copolymer vesicles, we present a straightforward sequential drug delivery system with dual-redox response that releases hydrophilic doxorubicin hydrochloride (DOX·HCl) and hydrophobic paclitaxel (PTX) under oxidative and reductive conditions, respectively. When compared to concurrent therapeutic delivery, the spatiotemporal control of drug release allows for an improved combination antitumor effect. The simple and smart nanocarrier has promising applications in the field of cancer therapy.