Background: After the closure of the African Programme for Onchocerciasis Control (APOC) in 2015, the Ministry of Public Health of Cameroon has continued implementing annual community-directed treatment with ivermectin (CDTI) in endemic areas. The World Health Organization has proposed that 12 countries be verified for elimination (interruption) of transmission by 2030. Using Rapid Epidemiological Mapping of Onchocerciasis, a baseline geostatistical map of nodule (onchocercoma) prevalence had been generated for APOC countries, indicating high initial endemicity in most regions of Cameroon. After more than two decades of CDTI, infection prevalence remains high in some areas. This study aimed at mapping the spatio-temporal evolution of Onchocerca volvulus prevalence from 1971 to 2020 to: i) identify such areas; ii) indicate where alternative and complementary interventions are most needed to accelerate elimination, and iii) improve the projections of transmission models. Methodology: A total of 1,404 georeferenced (village-level) prevalence surveys were obtained from published articles; the Expanded Special Project for Elimination of Neglected Tropical Diseases portal for Cameroon; independent researchers and grey literature. These data were used together with bioclimatic layers to generate model-based geostatistical (MBG) maps of microfilarial prevalence for 1971–2000; 2001–2010 and 2011–2020. Principal findings: Time-period was negatively and statistically significantly associated with prevalence. In 1971–2000 and 2001–2010, prevalence levels were high in most regions and ≥60% in some areas. Mean predicted prevalence declined in 2011–2020, reaching