Cross-Sectoral partnerships constitute an increasingly practiced yet less understood phenomenon. The mechanisms are studied through different disciplines in quite disparate manners, which has led to a lack of holistic understanding of how they function in real-life. Especially, their embeddedness in national contexts in developing countries has been less explored. This study sets out to generate an in-depth understanding of how actors interact in and around cross-sectoral partnership mechanisms in developing country settings. To this end, it undertakes a case study of the Global Fund’s Country Coordinating Mechanism (CCM) in Ethiopia. The study draws on the critical realism research paradigm, whereby it actively seeks to unravel the causal, contextual factors that underlie observed ways of interactions between actors. In this regard, the study deploys a guiding theoretical framework that directs the focus of the study towards understanding the interplay between actors’ agency and the 2-layered context of interaction, which is represented by the CCM’s regulatory frameworks and the deeper frames of reference in the Ethiopian setting. This qualitative study employed multiple methods of data collection including in-depth interviews with 43 policy makers, non-participant observation, and document review. The data is analysed through the thematic analysis method whereby themes are developed both apriori in view of the theoretical framework of the study and through identification and interpretation of emerging themes from the data. The findings reveal the contextual and process related factors that influence interactions between actors in and around the CCM in Ethiopia. Furthermore, the findings of the study expose the power relationships that underlie observed ways of interactions in the setting. By combining the context and process-orientated perspectives, the study offers a holistic account of how cross-sectoral interactions occur in a developing country setting. The analytical logics offered by the study, in terms of how the contextual and process related factors influence cross-sectoral interactions, provide testable propositions for future studies of cross-sectoral partnerships in developing country settings.