Background Evidence exists about synergies among universal health coverage, health security and health promotion. Uniting these three global agendas has brought success to the country’s health sector. This study aimed to document the efforts Ethiopia has made to apply nationally synergistic approaches uniting these three global health agendas. Our study is part of the Lancet Commission on synergies between these global agendas. Methods We employed a case study design to describe the synergistic process in the Ethiopian health system based on a review of national strategies and policy documents, and key informant interviews with current and former policymakers, and academics. We analyzed the “hardware” (using the World Health Organization’s building blocks) and the “software” (ideas, interests, and power relations) of the Ethiopian health system according to the aforementioned three global agendas. Results Fragmentation of health system primarily manifested as inequities in access to health services, low health workforce and limited capacity to implementation guidelines. Donor driven vertical programs, multiple modalities of health financing, and inadequate multisectoral collaborations were also found to be key features of fragmentation. Several approaches were found to be instrumental in fostering synergies within the global health agenda. These included strong political and technical leadership within the government, transparent coordination, and engagement of stakeholders in the process of priority setting and annual resource mapping. Furthermore, harmonization and alignment of the national strategic plan with international commitments, joint financial arrangements with stakeholders and standing partnership platforms facilitated efforts for synergy. Conclusions Ethiopia has implemented multiple approaches to overcome fragmentation. Such synergistic efforts of the primary global health agendas have made significant contributions to the improvement of the country’s health indicators and may promote sustained functionality of the health system.