Understanding how and why some firms are better than others at exploring and exploiting new business opportunities is a cutting-edge research problem. Our central thesis, that information technology (IT) performs a differential role in firms’ opportunity exploration and exploitation, led us to examine how IT influences exploration and exploitation of business opportunities. We tested the proposed theory using partial least squares on a combination of survey and secondary data from 203 large firms in Spain. We found that: (1) IT infrastructure provides the foundation to build business experimentation, and the flexibility to sense and explore business opportunities; and (2) IT infrastructure-enabled business flexibility helps firms to develop the operational proficiency to exploit business opportunities, and increase their performance. This research contributes to the field of Information Systems by explaining whether and how IT infrastructure influences the firm’s capabilities for opportunity exploration and exploitation. The managerial implications are also discussed.