Antimicrobial resistance (AMR) is a growing global public health threat. Furthermore, wastewater is increasingly recognized as a significant environmental reservoir for AMR. Wastewater is a complex mixture of organic and inorganic compounds, including antibiotics and other antimicrobial agents, discharged from hospitals, pharmaceutical industries, and households. Therefore, wastewater treatment plants (WWTPs) are critical components of urban infrastructure that play a vital role in protecting public health and the environment. However, they can also be a source of AMR. WWTPs serve as a point of convergence for antibiotics and resistant bacteria from various sources, creating an environment that favours the selection and spread of AMR. The effluent from WWTPs can also contaminate surface freshwater and groundwater resources, which can subsequently spread resistant bacteria to the wider environment. In Africa, the prevalence of AMR in wastewater is of particular concern due to the inadequate sanitation and wastewater treatment facilities, coupled with the overuse and misuse of antibiotics in healthcare and agriculture. Therefore, the present review evaluated studies that reported on wastewater in Africa between 2012 and 2022 to identify knowledge gaps and propose future perspectives, informing the use of wastewater-based epidemiology as a proxy for determining the resistome circulating within the continent. The study found that although wastewater resistome studies have increased over time in Africa, this is not the case in every country, with most studies conducted in South Africa. Furthermore, the study identified, among others, methodology and reporting gaps, driven by a lack of skills. Finally, the review suggests solutions including standardisation of protocols in wastewater resistome works and an urgent need to build genomic skills within the continent to handle the big data generated from these studies.