This study aimed to determine if implemented donor-funded health related-programs in Africa were sustained beyond the funding lifecycle and determine their facilitators and impeders. A systematic review was conducted after the documentation of a study protocol. A database search was done across three databases namely Google Scholar, PubMed, and Medline between January 27 and February 15, 2022. All peer-reviewed articles on sustainability of health interventions in Africa published between 2015 and 2021 that provided one or more context-relevant definitions of sustainability were included. Publications with no use of quantitative or qualitative methods and studies with no information on project evaluation after initial implementation were excluded. Screening of titles and abstracts was done, and the full texts of all relevant articles were retrieved. The risk of bias in systematic reviews (ROBIS) tool was used to assess the risk of bias in the systematic review. Overall, 4,876 articles were retrieved, and only nine articles were eligible for inclusion in the review following the removal of duplicates. Overall, sustainability was described in only three of the five regions in Africa. Donor-funded projects were sustained beyond the funding lifecycle in seven (77.8%) studies. Facilitators of sustainability in Africa included community ownership of the project through the engagement of community stakeholders in the design and implementation of such projects, use of locally available resources, sound infrastructure, and the constitution of interdisciplinary team to facilitate capacity building. Impeders to the sustainability of donor-funded projects included weak health systems exemplified in poor documentation and integration of records, lack of financial leadership, shortage of resources, political interference, poor feedback mechanism, and weak donor-community interactions. From the ROBIS tool, a low risk of bias existed in the studies included in the review. Although the included studies appropriately considered the review’s research question, seven studies had a low risk of bias in the domains one to three, and two studies had high risk of bias in domain four. To derive maximum benefits from donor-funded health interventions, sustainability of such projects is key. During program planning phase, context-based facilitators of sustainability should be promoted, while impeders are immediately addressed.