Onchocerciasis is a blindness-causing disease caused by a nematode called Onchocerca volvulus that is transmitted by Simulium blackflies. The disease is a major epidemiological problem among rural communities living in close proximity to rivers in some population in Sub-Saharan Africa. Recent studies identified Ghana to be a treat of recrudescence of onchocerciasis in neighboring countries. This thesis applies spatial models, predicts, and assesses population at risk of onchocerciasis in Ghana. It also evaluates the disease endemicity in Burundi in order to test the models applied in Ghana. Onchocerciasis prevalence data spanning a period of 2004 (Ghana) and 1985-1992 (Burundi) were integrated together with biophysical variables in a GIS. Next, modeling of the spatial risk of onchocerciasis was based on the principal component analysis (PCA) regression models. The final predictive spatial models represent the risk of the disease. The spatial models showed potential biogeographic zones and epidemiological patterns of onchocerciasis in relation to village settlements that are at risk. Also, the risk of onchocerciasis increased with the proximity to the rivers. The estimated population at risk in Ghana in 2010 was 5,211,808 people (or 21.36% of the total population) and 235,032 people in Burundi (or 2.8% of the total population). Findings from this study can help in the effective design of preventive control measures of the risk of recrudescence of the disease and safeguard the achievements of the OCP and APOC programs.