Food safety is a global concern in today’s world, and harnessing food safety in Sub-Saharan Africa, especially Nigeria and Ghana are momentous. This review presents an insight into the situation of food safety in Nigeria and Ghana. Using a desktop review technique, research papers were evaluated to find major sources of food safety concerns. It was revealed that many studies reported on food contamination at the consumption level whereas few reported on the healthiness of the production chain. Improper handling of food at the local markets, vending sites hygiene practices of food vendors, and bad transportation and packing systems have all been implicated. Inadequate education is a major cause of food contamination, especially at the consumption level. Again, etiologic agents responsible for food-borne illness in Ghana and Nigeria range from viruses, fungi, parasites, and protozoans to bacteria. They include rotavirus, hepatitis A virus, Lassa fever (LHF), human noroviruses (HNoV), Aspergillus parasiticus, Aspergillus flavus, Aspergillus niger, Taenia solium, Ascaris spp., Toxoplasma gondii, Cryptosporidium spp. Enterobacter spp., Pseudomonas spp., Campylobacter spp., Escherichia coli. Staphylococcus spp., Salmonella spp., Vibrio cholerae and Listeria monocytogenes. Their toxins are responsible for numerous food contaminants. Some foods are contaminated with chemicals including pesticide residues, lead, mercury, etc. Laws of food safety are not well enforced leading to complications in the food production chain. Rigorous monitoring and evaluation coupled with surveillance and education to harness the situation and detect issues that compromise the right process is a necessity. Finally, intentional enforcement of regulations by regulatory agencies will go a long way to curb food contamination and food-borne illnesses within the region.