There is a growing understanding that strong health systems are crucial to sustain progress. Health systems, however, are complex and much of their success depends on factors operating at different levels and outside the health system, including broader governance and political commitment to health and social development priorities. Recognizing these complexities, this article offers a pragmatic approach to exploring the drivers of progress in maternal and child health in Mozambique, Nepal and Rwanda. To do this, the article builds on a semi-systematic literature review and case study findings, designed and analysed using a multi-level framework. At the macro level, governance with effective and committed leaders was found to be vital for achieving positive health outcomes. This was underpinned by clear commitment from donors coupled by a significant increase in funding to the health sector. At the meso level, where policies are operationalized, inter-sectoral partnerships as well as decentralization and task-shifting emerged as critical. At micro (service interface) level, community-centred models and accessible and appropriately trained and incentivized local health providers play a central role in all study countries. The key drivers of progress are multiple, interrelated and transversal in terms of their operation; they are also in a constant state of flux as health systems and contexts develop. Without seeking to offer a blueprint, the study demonstrates that a ‘whole-system’ approach can help elicit the key drivers of change and potential pathways towards desirable outcomes. Furthermore, understanding the challenges and opportunities that are instrumental to progress at each particular level of a health system can help policy-makers and implementers to navigate this complexity and take action to strengthen health systems.