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Objective To determine seroprevalence , asses risk factors and active outbreaks investigation to identify theFMD virus using molecular tools Methods A cross sectional study was conducted from October 2018 to May 2019 to investigate the epidemiology of foot and mouth disease. A multistage sampling was implemented to determine seroprevalence and asses risk factors of foot and mouth disease. Additionally active outbreaks were investigated to identify the virus using molecular tools. Results Questionnaire survey was carried out and revealed that various factors affect the occurance of foot and mouth disease. Up on 3ABC ELISA analysis an overall prevalence of 24.39% (269/1103) in cattle and 2.11% (9/426) in pigs was observed. Multivariable logistic regression analysis showed statistically significant differences among districts: cattle from Bahir Dar Zuria, Bishoftu, Sodo Zuria and Gonder Zuria had less odds of being sero-positive with odds ratio of 0.56 (CI= 0.34-0.92), 0.23 (CI= 0.09-0.57), 0.22 (CI= 0.11-0.42) and 0.15 (CI= 0.09-0.27), respectively compared to cattle from Alage district. Pigs from Bishoftu were less likely to test postive than pigs from Addis Ababa with an odds ratio of 0.04 (95% CI= 0.01-0.34). Female and older cattle greater than 3 years have higher odds of being seropostive than their male and younger counterparts respectively. The molecular characterization revealed that FMDV virus genome was detected in 66.7% (46/69) of active outbreak samples by rRT-PCR targeting 3D region of the genome. Further, 9 samples were characterized by serotyping and sequencing and found that (6 serotype A African topotype of G-IV topotypes and 3 serotype O of EA-3(2) and EA-4(1) topotypes) were identified Conclusions The viruses isolated in this study were clustered with other African isolates. Thus, FMDV control strategy should be designed in such a way that implementation of appropriate biosecurity measures, regular serosurveilance and frequent outbreak investigation in function of effective vaccine design and vaccination. Financial Support VLIRUOS