Poor wastewater management remains a critical health and environmental challenge in most developing countries in Sub-Saharan Africa due to the lack of adequate infrastructure for collection and treatment. This study evaluated the performance and methane production of a full-scale upflow anaerobic sludge blanket (UASB) reactor of capacity 18000 m³/d, with post-treatment unit: trickling filters followed by final settling tanks for municipal wastewater treatment in Ghana. Data was collected on operational conditions and physicochemical parameters of wastewater (influent and effluent) over a period of 35 weeks in 2021 (from January to August). The influent biochemical oxygen demand to chemical oxygen demand (BOD:COD) ratio was 0.58 ± 0.16, indicating the presence of highly biodegradable compounds in the sewage. Operational conditions for the UASB reactors were observed to be within the optimal range for anaerobic systems, with an applied organic loading rate of 1.30 ± 0.79 kgCOD/m³/d. Generally, Plant performance was satisfactory with carbon removal at 93% for COD and 98% for BOD. Biogas yield was 0.2 m³/kgCOD removed, culminating in an average biogas production rate of 831.6 ± 292.7 m³/d. Average methane composition was 64.7 ± 11.9% of the biogas output, whilst an estimated 35% of the methane generated remained dissolved in the UASB effluent. The UASB reactor presents an efficient technology that can be implemented in developing countries for effective and sustainable wastewater management.