In the past two decades, community-based Health Insurance (CBHI) is expanding in most of sub-Saharan African countries with the aim of improving equitable access to health services for the informal sector population. However, population enrolment into CBHI and membership renewals thereafter remains stubbornly low. The purpose of this systematic review is to generate an evidence to better understand barriers to uptake of CBHI in sub-Saharan African countries. We systematically searched for relevant studies from databases: PubMed, Scopus, Cumulative Index of Nursing and Allied Health Literature (CINAHL), PsychInfo, ProQest, Excerpta Medica dataBASE (EMBASE) and Africa-Wide Information. The search strategy combined detailed terms related to (i) CBHI, (ii) enrolment/renewal and (iii) sub-Saharan African countries. A narrative synthesis of findings was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The protocol for this systematic review was registered with International Prospective Register of Systematic Reviews (PROSPERO) (ref: CRD42020183959). The database search identified 4055 potential references from which 15 articles reporting on 17 studies met the eligibility criteria. The findings revealed that barriers to uptake of CBHI in sub-Saharan Africa were multidimensional in nature. Lack of awareness about the importance of health insurance, socio-economic factors, health beliefs, lack of trust towards scheme management, poor quality of health services, perceived health status and limited health benefit entitlements were reported as barriers that affect enrolments into CBHI and membership renewals. The methodological quality of studies included in this review has been found to be mostly suboptimal. The overall findings of this systematic review identified major barriers of CBHI uptake in sub-Saharan African countries which may help policymakers to make evidence-informed decisions. Findings of this review also highlighted that further research with a robust methodological quality, depth and breadth is needed to help better understand the factors that limit CBHI uptake at individual, societal and structural levels in sub-Saharan Africa.