Significant scale-up of donors’ investments in health systems strengthening (HSS), and the increased application of harmonization mechanisms for jointly channelling donor resources in countries, necessitate the development of a common framework for tracking donors’ HSS expenditures. Such a framework would make it possible to comparatively analyse donors’ contributions to strengthening specific aspects of countries’ health systems in multi-donor-supported HSS environments. Four pre-requisite factors are required for developing such a framework: (i) harmonization of conceptual and operational understanding of what constitutes HSS; (ii) development of a common set of criteria to define health expenditures as contributors to HSS; (iii) development of a common HSS classification system; and (iv) harmonization of HSS programmatic and financial data to allow for inter-agency comparative analyses. Building on the analysis of these aspects, the paper proposes a framework for tracking donors’ investments in HSS, as a departure point for further discussions aimed at developing a commonly agreed approach. Comparative analysis of financial allocations by the Global Fund to Fight AIDS, Tuberculosis and Malaria and the GAVI Alliance for HSS, as an illustrative example of applying the proposed framework in practice, is also presented.