In 2018, 676.1 million people in Africa (52.5% of the population) were moderately or severely food insecure. This exceptionally high prevalence continues to increase as Africa experiences conflict, climate change, and economic declines. When Sustainable Development Goal 2.1 set out to end hunger and ensure access to sufficient food, particularly for vulnerable populations, by 2030, food insecurity emerged as a global priority. Food insecurity has been hypothesized to negatively impact mental health, a stigmatized area of health in Africa for which care is often inaccessible. This systematic review examines existing literature on the relationship between food insecurity and mental health in Africa, where progress remains to be made on both fronts. A systematic search of seven databases (EMBASE, Web of Science, CINAHL, PsychINFO ProQuest, Medline Ovid, Scopus, and Nursing and Allied Health) was conducted. Results were limited to studies examining food insecurity and mental health, written in English and published between January 2000 and May 2020. After title, abstract, full-text review, and quality appraisal using tools from the National Heart, Lung, and Blood Institute, 64 studies remained. Findings were summarized using a narrative synthesis approach. Studies unanimously highlighted that food insecurity is associated with poor mental health. This relationship was dose-responsive and independent of the measured mental health outcome. Two highly represented groups in the literature were women around pregnancy and people affected by HIV/AIDS. Factors which mediated the relationship included age, sex, social interactions, physical health, seasonality, and rural residence. The findings suggest that the relationship is likely amplified in specific populations such as women and seniors, and interventions which target livelihood as opposed to income may be more effective. Further research is needed which compares food insecurity's effect on mental health between at-risk populations, in order to guide resource allocation and context-specific policy making.