Based on the systems and control perspectives, this study develops a model to examine whether virtual integration enabled by information technology (IT) can facilitate manufacturers to achieve greater supply chain flexibility and comparative cost advantage in facing environmental uncertainty. Results show that environmental uncertainty tends to motivate manufacturers to increase their manufacturing flexibility, with both virtual integration and supplier responsiveness playing a vital, enabling role. The results also demonstrate the importance of supplier responsiveness for manufacturers to obtain manufacturing flexibility and comparative cost advantage in supply chain operations. The implications of the study are provided.