Foot and mouth disease is an extremely contagious transboundary disease of livestock that causes significant economic losses in Ethiopia. A cross sectional study was conducted from November 2018 to May 2019 to estimate seroprevalence and to assess associated risk factors in selected districts of afar region. Purposive and simple random sampling technique was employed to select the study areas and animals respectively. A total of 384 sera were collected from 72 herds and seroprevalence of the disease was determined using 3ABC-ELISA technique. Data generated from laboratory reports and questionnaire survey was recorded and coded using Microsoft Excel spreadsheet and analyzed using STATA version 14. Potential risk factors of the disease were also assessed using logistic regression analysis. Out of 384 sera tested, the overall seroprevalence of FMDV was 19.8% (n=76; 95% CI=15.8-23.79) at animal level and 56.94% at herd level. The herd level seroprevalence was higher in animals tested from Dubti (85%, n=17) than those from Asayita (48.13%, n=13) and Chifra (44%, n=11). Among the associated risk factors, age, herd size, district and contact with wild life were statistically associated with FMDV serostatus (P<0.05). Medium and large herd size animals were 2.49 (95% CI: 1.33-6.63) and 6.05(95% CI: 2.54-14.43) times more likely to develop the disease as compared to those animals from small herd size respectively. Adult cattle were 2.97 times more likely to have a chance of contracting the disease as compared to young cattle. The current study finding revealed that FMD was more prevalent and economically significant disease in the study districts. Hence, further studies ought to be conducted to estimate the region wise magnitude of the disease and to identify and characterize the circulating serotypes and strains in the areas.