Seroprevalence and Risk Factors of African Horse Sickness in Three Agroecological Zones of Cameroon

African horse sickness (AHS), a highly fatal arbovirosis of equines is endemic in sub-Saharan Africa. However, its epidemiology is poorly known in Cameroon. This study aimed to investigate the prevalence profile and risk factors of African horse sickness in Cameroon. Horse sera were subjected to the ELISA blocking test for the determination of antibodies against African horse sickness virus, and positive samples were submitted to capture ELISA to determine the presence of antigens. Potential risk factors associated with AHS were assessed based on the information collected in the field. The chi-square test and the odd ratio (OR) were used to test the association between serology and the different variables. Of the 336 sera obtained, 198 were positive for antibodies with a prevalence of 58.93% (CI: 53.67–64.19). From the 198 positive sera to antibodies, only one revealed positivity to antigens with a prevalence of 0.51% (CI: 0–1.5). Agroecological zone I (94.31%, CI: 91.83–96.79, OR: 34.92) was significantly (p < 0.05) associated with the higher risk of disease dissemination than agroecological zone II (66.67%, CI: 61.63–71.71, OR: 4.21) and agroecological zone III (32.18%, CI: 27.18–37.18; OR: 1). Males (63.59%, CI: 58.44–68.74, OR: 1) were significantly (p < 0.05) affected than females (50.42%, CI: 45.07–55.77; OR: 0.58). Horses of more than 8 years (76.00%, CI: 71.43–80.57) were significantly (p < 0.05) at risk than young animals of less than 3 years old (32.14%, CI: 27.15–37.13, OR: 0.15). This study highlights a high seroprevalence of antibodies of African horse sickness in Cameroon. Agroecological zone, age, and the importation of horses were highly associated with the distribution of disease at the national level.