In the face of an external environment featuring a high level of risk, multiple changes, and high uncertainty, the supply chain’s emergency replenishment, collaborative management, regulation of organic commodity, and low-cost rapid response will promote its’ sustainable growth and development, which is necessary for today’s economic development. The digitization and flexibility of the supply chain are of great value in obtaining the sustainable development of the supply chain. When dealing with an uncertain environment and market risk, current supply chain flexibility not only functions through its internal organizational flexibility, but also through collaborative creation and an extended supply chain network which will proactively form a replenishment supply sub-chain driven by the need for change responsiveness. This article constructs an associated model consisting of digitization, supply chain flexibility, and sustainability using an empirical analysis method to explore the implicit correlation of these factors. The analysis results of the mediating effect model show that both digitization and flexibility have significant positive effects on the sustainable development of the supply chain. Collaborative knowledge creation and supply chain flexibility play multiple mediating roles while market uncertainty positively moderates the impact of supply chain flexibility on supply chain sustainable development.