Cross-sectional study was conducted from December, 2008 to April, 2009 to determine the sero prevalence of foot and mouth disease (FMD) virus in West and South West Shoa zones of Oromia regional state, central Ethiopia. The samples were processed with the 3 ABC ELISA kits that can able to identify natural infected animal from vaccinated animals. From the total sera of 421 tested, the overall sero prevalence of FMD in cattle was 15.0% (63/421). The prevalence rate was higher (22%) in the South west shoa zone than West shoa zone (5.6%). The difference was statistically significant (ρ<0.05). At district level, the highest sero prevalence were recorded at Dawo (26.7%), Alemgana (26.2%), Kokir (24.4%) and Haramaya (21.4%) districts, which were located at south west shoa zone. The difference among districts were statistically significant (ρ<0.05). Statistically difference was also observed between different age groups (ρ<0.05); being higher in adult (19.3%) followed by calves (9.3%). The sero prevalence of male and female were 16.0 and 14.1%, respectively, and which was not statistically significant (ρ>0.05). The sero prevalence of FMD was found higher in mid highland (16.8%) than highland attitude (6.7%) which was statistically significant (ρ<0.05). The result of this study indicated that FMD is highly prevalent in the South West Shoa zone than West Shoa zone due to contact of different origin of animals, and free animals movement in search of feed and water in zone. Age and attitude were also found as an important risk factor for the diseases. Finally, it is recommended that, sero typing of the virus circulating in the study area should be undertaken for effective control of the disease.