Vaccines and vitamin A supplementation are financed by donors in several countries, indicating that challenges remain with achieving sustainable government financing of these critical health commodities. This qualitative study aimed to explore political economy variables of actors’ interests, roles, power, and commitment to ensure government financing of vaccines and vitamin A supplementation (VAS). A total of 77 interviews were conducted in Burundi, Comoros, Ethiopia, Madagascar, Malawi, and Zimbabwe. Governments and development partners had similar interests. Donor commitment to vaccines and VAS was sometimes dependent on the priorities and political situation of the donor country. Governments’ commitment to financing vaccines was demonstrated through policy measures, such as enactment of immunization laws. Explicit government financial commitment to VAS was absent in all six countries. Some development partners were able to influence governments directly via allocation of health funding while others influenced indirectly through coordination, consolidation, and networks. Government power was exercised through multiple systemic and individual processes, including hierarchy, bureaucracy in governance and budgetary process, proactiveness of Ministry of Health officials in engaging with Ministry of Finance, and control over resources. Enablers that were likely to increase government commitment to financing vaccines and VAS included emerging reforms, attention to the voice of citizens, and improvements in the domestic economy that in turn increased government revenues. Barriers identified were political instability, health sector inefficiencies, overly complicated bureaucracy, frequent changes of health sector leadership, and non-health competing needs. Country governments were aware of their role in financing vaccines, but only a few had made tangible efforts to increase government financing. Discussions on government financing of VAS were absent. Development partners continue to influence government health commodity financing decisions. The political economy environment and contextual factors work together to facilitate or impede domestic financing.