Digital transformation (DT) has become essential for higher education institutions (HEIs), with its value becoming increasingly evident since the COVID-19 pandemic. This holds true for HEIs in developing countries as well, where DT is a strategic priority despite the challenges posed by the digital divide. Leadership is recognized as both a critical factor and a prerequisite for successful implementation of DT in HEI within such contexts. This study explored challenges and leadership responses that facilitate successful DT implementation in the context of Ghanaian HEIs. The study aims to offer insights for policymakers, administrators, and stakeholders within African HEIs, to facilitate the development of contextually relevant and effective DT strategies. Employing a qualitative multiple case study approach, data was collected through semistructured interviews with senior administrators leading Open, Distance, and Digital Education (ODDE) implementation at three Ghanaian public universities. Thematic and content analysis were then used to analyze the interview data. The findings revealed that the universities were driven to pursue DT initiatives by both internal demands (e.g., to improve existing service delivery through technology) and external pressures to use the affordances of technology to increase access and participation through non-traditional learning modes. Despite facing structural, technological, and human resource challenges, the study observed positive signs of leadership-enabled DT initiatives to support post-COVID-19 efforts. However, these efforts have unfolded within a less coordinated policy climate and have been predominantly driven topdown, with Vice-Chancellors initiating and spearheading digital leadership responses. Meanwhile, there was little evidence of cross-cutting leadership across the universities to support DT efforts. The study concludes by arguing for the contextualisation of DT in higher education and offers suggestions for university leaders in Ghana and other relevant developing contexts to enhance their DT efforts.