Understanding the formation of supply chain flexibility is important. We draw on the organizational learning perspective to examine how inter-organizational systems (IOS) enabled collaborative knowledge creation can enhance the supply chain flexibility. Empirical results from 141 supply chain enterprises support most of our hypotheses. The results show that, (1) IOS use for exploration has positive effects on supply chain flexibility and collaborative knowledge creation plays a partially mediated role between them; (2) Market uncertainty moderates the relationship between IOS use for exploration for collaborative knowledge creation. And (3) under the greater uncertainty in the market environment, the relationship between company's collaborative knowledge creation and supply chain flexibility becomes stronger. This result suggests when supply chain enterprises face market uncertainty, they need to improve the level of IOS use for exploration to facilitate understanding of the market, which will improve the supply chain flexibility.