Information technology (IT)-business alignment continues to be a challenge for businesses. A potential reason may be the absence of relevant IT leadership capable of engaging IT and business units in a way that leads to alignment. Based on the knowledge integration view of organizations and the strategic leadership literature, we propose a model linking chief information officer (CIO) leadership style to IT-business alignment. We examine how ambidextrous CIO leadership behavior influences IT-business alignment through knowledge integration mechanisms, namely mechanisms that develop shared domain knowledge between IT and business specialists and mechanisms for collaborative integration of specialized IT and business knowledge. Analysis of cross-industry data collected from CIOs, top management team members, and IT specialists indicates that CIOs who can display both transformational and transactional leadership promote these mediating mechanisms. Moreover, the results show that these mechanisms have a substitutive effect, in that the effect of one mechanism diminishes when the other exists at a high level.