Honey is commonly used as a food sweetener in Ghana and it is one of the most important food products with enormous nutritive benefits. In recent times, the increasing concern about sugar related diseases such as diabetes has led to increased consumption of honey in Ghana. This study assessed the physico-chemical properties and microbiological quality of honey collected from supermarkets and apiaries across six major agro-ecological zones of Ghana. In all, 57 honey samples were analyzed for pH, colour, solid sugars and moisture contents, whereas 46 samples were assessed for their microbiological status. The results showed that honey produced in Ghana had significantly wider variations in pH, moisture (p=0.000), solid sugar (0.000) and RI (0.000) within and across the six agro-ecological zones. Similarly, wider variations of these indices occurred between honey harvested from single hives and the admixtures. The results also showed that most of the honey produced in Ghana are characteristically amber in colour, while fewer samples appear black. Honey from the Northern region had the widest variation in colour, ranging from light amber to black. Most of the honeys studied (66.7% of samples) contained solid sugar contents which is either below the CODEX Alimentarius recommendation of 80 %, while 33.3% of the samples contained levels within the recommended ranges. Moreover, the admixture had higher solid sugar contents than single hive honey. About 66% of the honey studied had moisture content above the 20% recommended by USDA and Codex Alimentarius. In addition, the single hive honeys had higher moisture contents than the admixture honeys. The results also revealed that admixtures possess higher RIs than single hive honey. The honey samples assessed in this study were contaminated with bacteria (Bacillus licheniformis, Bacillus subtilis, Citrobacter amalonaticus, Escherichia coli, Micrococcus luteus, Providencia rettgeri, Staphylococcus aureus and Streptococcus faecalis) and fungi genera Aspergillus, Penicillium, and Mucor. Further, 45% of the total samples were above the USDA acceptable limits of microorganisms considered safe for foods and honey. Moreover, significant levels of bacterial and fungal contamination of honey samples; significantly high means of bacterial counts were observed in honey from both admixture and apiaries than fungi. Interestingly, Clostridium botulinum was isolated from a few samples of honey. Only 7% of the total honey samples from Greater Accra, Western, Volta, Eastern and Northern regions contained Clostridium botulinum and this was the first time this organism is being reported in the country. However, contamination levels were below USDA acceptable limits of 1 x 104 CFU per gram for detected samples. Therefore, the honey studied can be considered safe for consumption. This notwithstanding, the study has demonstrated the need for monitoring the quality of honey produced in the country to ensure the safety of consumers.