Health system governance has to do with decision-making – who makes decisions, when, where, how and why. At the district level – the level of care which operationalises health policies – governance is critical, yet remains little understood. Governance has the ability to influence health system performance, and this is essential in maternal and newborn health, where timely decisions are required to support policy implementation. In this regard, district managers are particularly important. They are the link in the middle of the health system, connecting top-end policy formulation to bottom-end implementation. Their abilities to interpret, translate, support and challenge policy will have an effect on what gets operationalised. However, capacity weaknesses in district management and leadership are often cited as a factor in poor health system performance. This thesis seeks to deepen understandings of district-level management, leadership and decision-making for policy and programme management and implementation for maternal and newborn health. Within this, the thesis also seeks to understand the scope for change that an intervention to strengthen management and leadership capacities can bring. This thesis contributes to the applied field of health policy and systems research by drawing on policy implementation theory, organisational management theory and complexity theory as its theoretical basis. A realist approach methodology was undertaken to understand the contexts in which district managers are embedded, how this influences their decision-making, and what the effects of a managerial intervention are, given these contexts. The thesis followed an embedded case study flexible design. The first case study was an exploratory qualitative case study to understand how and why district managers make decisions in maternal and newborn health policy implementation. The second case study was an historical case study of district manager decision-space over time. The third case study was an explanatory qualitative case study of the management and leadership intervention. The final validation of our theorising throughout the cases was achieved through the administration of a questionnaire across all district health management teams of the Great Accra Region. This thesis demonstrates that district managers find themselves in contexts of strong hierarchical authority and resource uncertainty – in particular, lacking financial transparency. This promotes a management and leadership typology which attunes managers towards serving the health system bureaucracy, resulting in reduced district-level responsiveness to maternal and newborn health challenges. The outcome is that district manager decision-space is narrow surrounding resource allocation decisions, and this in turn affects local planning programming and management. The thesis further demonstrates that broader patterns of centralised governmental decision-making have affected the development of the district health system over time. Particularly, the sequencing of decentralisation processes has ensured that national-level decision-making has remained empowered in contrast to district-level decision-making. System fragmentation – through reduced Government of Ghana funds and increasingly verticalised donor funds – has also been a contributor. This accounts for the observed hierarchical authority and resource uncertainty which affects district managers. As a result of these contexts, this thesis also showed that an intervention to strengthen management and leadership capacities was limited in its sustainability. This thesis raises the issues of health system organisation as critical to the potential of district management and leadership effectiveness. It provides evidence that weaknesses in district management and leadership arise out of the organisational governance mismatches in autonomy and responsibility. It suggests that in strengthening management and leadership, approaches which seek to address organisational capacities, not only individual capacities, are needed to convey sustainable change. Advancements in this regard have the scope to improve district manager decision-making for maternal and newborn health policy and programme implementation in the future.