Background Currently, sub-Saharan Africa (SSA) is experiencing a steady increase in the prevalence of diabetes mellitus (DM) coupled with a prevailing high burden of communicable diseases. To effectively address this burgeoning burden of DM, optimal access to affordable essential medicines and diagnostic tests for DM in healthcare systems should be prioritised. We conducted a systematic review of the evidence on the availability and affordability of essential medicines and diagnostic tests for DM in SSA as recommended by the World Health Organization Package of Essential Non-communicable Disease Interventions for Primary Health Care in Low-Resource Settings. Methods PubMed, Science Direct and African Journals Online databases were searched for original research articles conducted in sub-Saharan Africa and published between 2000 and 2018 reporting availability and affordability of essential medicines and diagnostic tests for diabetes mellitus. Results Twenty one original cross-sectional studies were included in the systematic review, with the majority conducted in Eastern Africa (n=11, 58%). The availability of essential medicines and diagnostic tests was largely sub-optimal. For oral hypoglycaemic agents and insulin, angiotensin-converting-enzyme inhibitors, statins and aspirin, availability ranged from 0-100%, 0-96.5%, 0-84% and 53%-100% respectively. Considering diagnostic tests, availability of blood glucose tests, urine protein and ketone tests, serum creatinine tests, lipid profile tests and electrocardiography ranged from 6-100%, 33.3-100%, 0-86.4%, 0-65.9% and 5.7-54.6% respectively. The lowest priced generic (LPG) glibenclamide, metformin and aspirin cost <1.2 days’ wages. However, the cost of LPG insulin (any type), captopril and simvastatin ranged from 3.85-18.7 days’ wages, 1.2-6.41 days’ wages and 6.5-30 days’ wages respectively. Blood glucose tests, urine protein and ketone tests and serum creatinine tests cost <3.3 days’ wages. Conclusions Optimal access to affordable essential medicines and diagnostic tests for DM remains a significant challenge in SSA. This represents a significant barrier towards the attainment of sustainable development goals and universal health coverage. Pragmatic region-specific solutions are urgently needed to address this challenge.