The study was conducted from October 2014 to June 2015 to estimate tick prevalence and identify major tick genera infesting cattle and the associated risk factors in Arbegona district, southern Ethiopia. A total of 2024 adult ticks were collected from main body parts of animals and eight species of ticks which belong to three genera were identified. Questionnaire survey was employed concerning the general case on the tick infestation problems on the cattle. From 384 cattle examined, 291 (75.7%) were found to be infested with one or more types of tick species. The relative prevalence of each genera was Amblyomma (34.9%), Rhipicephalus (Boophilus) (26.6%), Hyalomma (19.2%), and Rhipicephalus (19%). The prevalence of tick infestation in good (65.5%), medium (74%), and poor body condition animal (100%) was found to be statistically significant (p < 0.05). There was also significantly (p < 0.05) higher prevalence in old (98.4%) than adult (78.8%) and young (59.8%) age groups of animals. In the survey, 87.5% of respondents believe that there was tick infestation problem in their locality. This study showed there was high burden and prevalence of ticks that still play major roles in reducing productivity and cause health problems of cattle in the area which call for urgent attention.