A cross-sectional study was carried out in Nyangatom wereda of South Omo zone, Southern Nation and Nationalities People Region (SNNPR), Ethiopia with the general objectives to find out the prevalence of bovine trypanosomiasis and the risk factors associated with its prevalence from January to June 2015. To identify the protozoa blood samples (n =384) collected from the marginal ear vein of indigenous zebu cattle of more than one year age and both the sexes from three kebeles were examined by buffy coat technique, direct blood smear, thick blood smear and thin blood smear after staining. The overall prevalence of bovine trypanosomaisis was 26.3%. On peasant associations (PA'S) basis Lebere kebele has the highest prevalence 39(30.5%) followed by Shenkora kebele 34 (26.6%) and Ayipa kebele 28 (21.9%). Trypanosoma congolense is the most prevalent species (14.3%) followed by Trypanosoma vivax (5.70%) and Trypanosoma brucei (5.50%). A significant association was observed (P<0.05) between the disease positivity and age, sex and body condition score. The prevalence of trypanosomiasis was 16.20 and 31.50% in young and adult respectively. The prevalence 42.80 and 16.30 % in poor and good body condition score respectively. There was significant association between the risk factors and the species of trypanosomiasis (P<0.05). The result of the present study revealed that trypanosomiasis is the most important problem for animal production in the study area. Strategic control of bovine trypanosomiasis should be strengthened to improve livestock production and agricultural development in the area.